Journal articles: 'Amyloid Fibril Inhibition'

1

Šneideris, Tomas, Lina Baranauskienė, Jonathan G. Cannon, Rasa Rutkienė, Rolandas Meškys, and Vytautas Smirnovas. "Looking for a generic inhibitor of amyloid-like fibril formation among flavone derivatives." PeerJ 3 (September 24, 2015): e1271. http://dx.doi.org/10.7717/peerj.1271.

Full text

Abstract:

A range of diseases is associated with amyloid fibril formation. Despite different proteins being responsible for each disease, all of them share similar features including beta-sheet-rich secondary structure and fibril-like protein aggregates. A number of proteins can form amyloid-like fibrilsin vitro, resembling structural features of disease-related amyloids. Given these generic structural properties of amyloid and amyloid-like fibrils, generic inhibitors of fibril formation would be of interest for treatment of amyloid diseases. Recently, we identified five outstanding inhibitors of insulin amyloid-like fibril formation among the pool of 265 commercially available flavone derivatives. Here we report testing of these five compounds and of epi-gallocatechine-3-gallate (EGCG) on aggregation of alpha-synuclein and beta-amyloid. We used a Thioflavin T (ThT) fluorescence assay, relying on halftimes of aggregation as the measure of inhibition. This method avoids large numbers of false positive results. Our data indicate that four of the five flavones and EGCG inhibit alpha-synuclein aggregation in a concentration-dependent manner. However none of these derivatives were able to increase halftimes of aggregation of beta-amyloid.

APA, Harvard, Vancouver, ISO, and other styles

2

HOWLETT, David R., Amanda E. PERRY, Fiona GODFREY, Jane E. SWATTON, Kevin H. JENNINGS, Claus SPITZFADEN, Harry WADSWORTH, Stephen J. WOOD, and Roger E. MARKWELL. "Inhibition of fibril formation in β-amyloid peptide by a novel series of benzofurans." Biochemical Journal 340, no. 1 (May 10, 1999): 283–89. http://dx.doi.org/10.1042/bj3400283.

Full text

Abstract:

A series of benzofuran derivatives have been identified as inhibitors of fibril formation in the β-amyloid peptide. The activity of these compounds has been assessed by a novel fibril-formation-specific immunoassay and for their effects on the production of a biologically active fibril product. The inhibition afforded by the compounds seems to be associated with their binding to β-amyloid, as identified by scintillation proximity binding assay. Binding assays and NMR studies also indicate that the inhibition is associated with self-aggregation of the compounds. There is a close correlation between the activity of the benzofurans as inhibitors of fibril formation and their ability to bind to β-amyloid. Non-benzofuran inhibitors of the fibril formation process do not seem to bind to the same site on the β-amyloid molecule as the benzofurans. Thus a specific recognition site might exist for benzofurans on β-amyloid, binding to which seems to interfere with the ability of the peptide to form fibrils.

APA, Harvard, Vancouver, ISO, and other styles

3

Saelices, Lorena, Kevin Chung, Ji H. Lee, Whitaker Cohn, Julian P. Whitelegge, Merrill D. Benson, and David S. Eisenberg. "Amyloid seeding of transthyretin by ex vivo cardiac fibrils and its inhibition." Proceedings of the National Academy of Sciences 115, no. 29 (June 28, 2018): E6741—E6750. http://dx.doi.org/10.1073/pnas.1805131115.

Full text

Abstract:

Each of the 30 human amyloid diseases is associated with the aggregation of a particular precursor protein into amyloid fibrils. In transthyretin amyloidosis (ATTR), mutant or wild-type forms of the serum carrier protein transthyretin (TTR), synthesized and secreted by the liver, convert to amyloid fibrils deposited in the heart and other organs. The current standard of care for hereditary ATTR is liver transplantation, which replaces the mutantTTRgene with the wild-type gene. However, the procedure is often followed by cardiac deposition of wild-type TTR secreted by the new liver. Here we find that amyloid fibrils extracted from autopsied and explanted hearts of ATTR patients robustly seed wild-type TTR into amyloid fibrils in vitro. Cardiac-derived ATTR seeds can accelerate fibril formation of wild-type and monomeric TTR at acidic pH and under physiological conditions, respectively. We show that this seeding is inhibited by peptides designed to complement structures of TTR fibrils. These inhibitors cap fibril growth, suggesting an approach for halting progression of ATTR.

APA, Harvard, Vancouver, ISO, and other styles

4

Hasanbašić, Samra, Alma Jahić, Selma Berbić, Magda Tušek Žnidarič, and Eva Žerovnik. "Inhibition of Protein Aggregation by Several Antioxidants." Oxidative Medicine and Cellular Longevity 2018 (2018): 1–12. http://dx.doi.org/10.1155/2018/8613209.

Full text

Abstract:

Amyloid fibril formation is a shared property of all proteins; therefore, model proteins can be used to study this process. We measured protein aggregation of the model amyloid-forming protein stefin B in the presence and absence of several antioxidants. Amyloid fibril formation by stefin B was routinely induced at pH 5 and 10% TFE, at room temperature. The effects of antioxidants NAC, vitamin C, vitamin E, and the three polyphenols resveratrol, quercetin, and curcumin on the kinetics of fibril formation were followed using ThT fluorescence. Concomitantly, the morphology and amount of the aggregates and fibrils were checked by transmission electron microscopy (TEM). The concentration of the antioxidants was varied, and it was observed that different modes of action apply at low or high concentrations relative to the binding constant. In order to obtain more insight into the possible mode of binding, docking of NAC, vitamin C, and all three polyphenols was done to the monomeric form of stefin B.

APA, Harvard, Vancouver, ISO, and other styles

5

Selig, Emily E., Courtney O. Zlatic, Dezerae Cox, Yee-Foong Mok, Paul R. Gooley, Heath Ecroyd, and Michael D. W. Griffin. "N- and C-terminal regions of αB-crystallin and Hsp27 mediate inhibition of amyloid nucleation, fibril binding, and fibril disaggregation." Journal of Biological Chemistry 295, no. 29 (May 16, 2020): 9838–54. http://dx.doi.org/10.1074/jbc.ra120.012748.

Full text

Abstract:

Small heat-shock proteins (sHSPs) are ubiquitously expressed molecular chaperones that inhibit amyloid fibril formation; however, their mechanisms of action remain poorly understood. sHSPs comprise a conserved α-crystallin domain flanked by variable N- and C-terminal regions. To investigate the functional contributions of these three regions, we compared the chaperone activities of various constructs of human αB-crystallin (HSPB5) and heat-shock 27-kDa protein (Hsp27, HSPB1) during amyloid formation by α-synuclein and apolipoprotein C-II. Using an array of approaches, including thioflavin T fluorescence assays and sedimentation analysis, we found that the N-terminal region of Hsp27 and the terminal regions of αB-crystallin are important for delaying amyloid fibril nucleation and for disaggregating mature apolipoprotein C-II fibrils. We further show that the terminal regions are required for stable fibril binding by both sHSPs and for mediating lateral fibril–fibril association, which sequesters preformed fibrils into large aggregates and is believed to have a cytoprotective function. We conclude that although the isolated α-crystallin domain retains some chaperone activity against amyloid formation, the flanking domains contribute additional and important chaperone activities, both in delaying amyloid formation and in mediating interactions of sHSPs with amyloid aggregates. Both these chaperone activities have significant implications for the pathogenesis and progression of diseases associated with amyloid deposition, such as Parkinson's and Alzheimer's diseases.

APA, Harvard, Vancouver, ISO, and other styles

6

Xun, Tianrong, Wenjuan Li, Jinquan Chen, Fei Yu, Wei Xu, Qian Wang, Ruizhe Yu, et al. "ADS-J1 Inhibits Semen-Derived Amyloid Fibril Formation and Blocks Fibril-Mediated Enhancement of HIV-1 Infection." Antimicrobial Agents and Chemotherapy 59, no. 9 (June 8, 2015): 5123–34. http://dx.doi.org/10.1128/aac.00385-15.

Full text

Abstract:

ABSTRACTSemen-derived enhancer of viral infection (SEVI) is composed of amyloid fibrils that can greatly enhance HIV-1 infectivity. By its cationic property, SEVI promotes viral sexual transmission by facilitating the attachment and internalization of HIV-1 to target cells. Therefore, semen-derived amyloid fibrils are potential targets for microbicide design. ADS-J1 is an anionic HIV-1 entry inhibitor. In this study, we explored an additional function of ADS-J1: inhibition of SEVI fibril formation and blockage of SEVI-mediated enhancement of viral infection. We found that ADS-J1 bound to an amyloidogenic peptide fragment (PAP248–286, comprising amino acids 248 to 286 of the enzyme prostatic acid phosphatase), thereby inhibiting peptide assembly into amyloid fibrils. In addition, ADS-J1 binds to mature amyloid fibrils and antagonizes fibril-mediated enhancement of viral infection. Unlike cellulose sulfate, a polyanion that failed in clinical trial to prevent HIV-1 sexual transmission, ADS-J1 shows no ability to facilitate fibril formation. More importantly, the combination of ADS-J1 with several antiretroviral drugs exhibited synergistic effects against HIV-1 infection in semen, with little cytotoxicity to vaginal epithelial cells. Our results suggest that ADS-J1 or a derivative may be incorporated into a combination microbicide for prevention of the sexual transmission of HIV-1.

APA, Harvard, Vancouver, ISO, and other styles

7

AITKEN, Jacqueline F., Kerry M. LOOMES, Barbara KONARKOWSKA, and Garth J. S. COOPER. "Suppression by polycyclic compounds of the conversion of human amylin into insoluble amyloid." Biochemical Journal 374, no. 3 (September 15, 2003): 779–84. http://dx.doi.org/10.1042/bj20030422.

Full text

Abstract:

There is a significant correlation between the occurrence of pancreatic islet amyloid and β-cell failure in advanced type II diabetes mellitus. Islet amyloid is composed primarily of the fibrillar form of the pancreatic hormone, amylin. Using thioflavin-T fluorescence binding and radioprecipitation assays, we investigated whether or not a series of small tricyclic compounds, tetracycline or Congo Red could interfere with the conversion of synthetic human amylin into its insoluble amyloid form. Of the compounds investigated, incubation of human amylin with a 20-fold molar excess of either Congo Red or Acridine Orange resulted in significant inhibition in the rate of amyloid formation. With Congo Red, maximal inhibition effectively occurred at a 1:1 molar ratio or greater over human amylin, whereas inhibition by Acridine Orange was dose-dependent. A 20-fold molar excess of the compound tetracycline also decreased insoluble amyloid content after extended incubation periods of approx. 20 h. Amyloid fibril morphology in the presence of tetracycline, as measured by transmission electron microscopy, was characterized by short fragmented fibrils compared with the longer and denser appearance of fibrils formed by amylin alone. These findings show that polycyclic compounds can suppress the formation of amyloid by human amylin, providing support for an alternative approach to peptide-based strategies by which islet amyloid formation could be modulated.

APA, Harvard, Vancouver, ISO, and other styles

8

Okumura, Hisashi, and Satoru G. Itoh. "Molecular Dynamics Simulation Studies on the Aggregation of Amyloid-β Peptides and Their Disaggregation by Ultrasonic Wave and Infrared Laser Irradiation." Molecules 27, no. 8 (April 12, 2022): 2483. http://dx.doi.org/10.3390/molecules27082483.

Full text

Abstract:

Alzheimer’s disease is understood to be caused by amyloid fibrils and oligomers formed by aggregated amyloid-β (Aβ) peptides. This review article presents molecular dynamics (MD) simulation studies of Aβ peptides and Aβ fragments on their aggregation, aggregation inhibition, amyloid fibril conformations in equilibrium, and disruption of the amyloid fibril by ultrasonic wave and infrared laser irradiation. In the aggregation of Aβ, a β-hairpin structure promotes the formation of intermolecular β-sheet structures. Aβ peptides tend to exist at hydrophilic/hydrophobic interfaces and form more β-hairpin structures than in bulk water. These facts are the reasons why the aggregation is accelerated at the interface. We also explain how polyphenols, which are attracting attention as aggregation inhibitors of Aβ peptides, interact with Aβ. An MD simulation study of the Aβ amyloid fibrils in equilibrium is also presented: the Aβ amyloid fibril has a different structure at one end from that at the other end. The amyloid fibrils can be destroyed by ultrasonic wave and infrared laser irradiation. The molecular mechanisms of these amyloid fibril disruptions are also explained, particularly focusing on the function of water molecules. Finally, we discuss the prospects for developing treatments for Alzheimer’s disease using MD simulations.

APA, Harvard, Vancouver, ISO, and other styles

9

Bhasikuttan, Achikanath C., and Jyotirmayee Mohanty. "Detection, inhibition and disintegration of amyloid fibrils: the role of optical probes and macrocyclic receptors." Chemical Communications 53, no. 19 (2017): 2789–809. http://dx.doi.org/10.1039/c6cc08727b.

Full text

Abstract:

This article provides a brief account of the recent reports on the early detection of amyloid fibril formation using fluorescent dyes and inhibition and disintegration of fibrils using macrocyclic receptors, which find applications in the treatment of fibril associated neurodegenerative diseases.

APA, Harvard, Vancouver, ISO, and other styles

10

Sandhya A, Gomathi Kanayiram, Kiruthika L, and Aafreen Afroz S. "Nigella Sativa : A Potential Inhibitor for Insulin Fibril Formation." International Journal of Research in Pharmaceutical Sciences 11, no. 1 (January 23, 2020): 765–74. http://dx.doi.org/10.26452/ijrps.v11i1.1891.

Full text

Abstract:

The high order structure from proteins which are self-assembled are known as fibrils. They are collectively called as amyloid fibrils, which generally lead to neurodegenerative diseases like Alzheimer's, Parkinson's, Huntington's, Type II diabetes. Insulin fibril aggregation is identified to be the major cause of neurodegenerative diseases. The effect of Nigella sativa extract is analyzed based on the fibril inhibition process. The formed fibrils is reduced with the concentration increase of Nigella sativa extract. Insulin fibril is found in Type II diabetes patients after repeated insulin injections subcutaneously. Insulin fibrils are formed in organisms or humans irrespective of their places like hips, shoulder, hands and abdomen. These are evident from the anti-aggregation assay. Thioflavin T (ThT) fluroscence and congo red (CR) assay confirms the inhibition of insulin fibril in the presence of Nigella sativa (NS) extract. Further, inhibition of fibril was confirmed by Scanning Electron Microscope (SEM), where no insulin fibrils was detected whose secondary conformational changes are studied using Fourier Transform Infrared spectroscopy (FT-IR). It is confirmed that insulin fibril inhibition depends on the various concentration of Nigella sativa. Based on the results obtained, it is demonstrated that Nigella sativa extract inhibits the fibril formation and it also provides a therapeutic strategy to prevent insulin fibril formation.

APA, Harvard, Vancouver, ISO, and other styles

11

Meier, Juris J., Rakez Kayed, Chia-Yu Lin, Tatyana Gurlo, Leena Haataja, Sajith Jayasinghe, Ralf Langen, Charles G. Glabe, and Peter C. Butler. "Inhibition of human IAPP fibril formation does not prevent β-cell death: evidence for distinct actions of oligomers and fibrils of human IAPP." American Journal of Physiology-Endocrinology and Metabolism 291, no. 6 (December 2006): E1317—E1324. http://dx.doi.org/10.1152/ajpendo.00082.2006.

Full text

Abstract:

Type 2 diabetes mellitus (T2DM) is characterized by an ∼60% deficit in β-cell mass, increased β-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). Human IAPP (hIAPP) forms oligomers, leading to either amyloid fibrils or toxic oligomers in an aqueous solution in vitro. Either application of hIAPP on or overexpression of hIAPP in cells induces apoptosis. It remains controversial whether the fibrils or smaller toxic oligomers induce β-cell apoptosis. Rifampicin prevents hIAPP amyloid fibril formation and has been proposed as a potential target for prevention of T2DM. We examined the actions of rifampicin on hIAPP amyloid fibril and toxic oligomer formation as well as its ability to protect β-cells from either application of hIAPP or endogenous overexpression of hIAPP (transgenic rats and adenovirus-transduced β-cells). We report that rifampicin (Acocella G. Clin Pharmacokinet 3: 108–127, 1978) prevents hIAPP fibril formation, but not formation of toxic hIAPP oligomers (Bates G. Lancet 361: 1642–1644, 2003), and does not protect β-cells from apoptosis induced by either overexpression or application of hIAPP. These data emphasize that toxic hIAPP oligomers, rather than hIAPP fibrils, initiate β-cell apoptosis and that screening tools to identify inhibitors of amyloid fibril formation are likely to be less useful than those that identify inhibitors of toxic oligomer formation. Finally, rifampicin and related molecules do not appear to be useful as candidates for prevention of T2DM.

APA, Harvard, Vancouver, ISO, and other styles

12

Xu, Sherry C. S., Josephine G. LoRicco, Anthony C. Bishop, Nathan A. James, Welby H. Huynh, Scott A. McCallum, Nadia R. Roan, and George I. Makhatadze. "Sequence-independent recognition of the amyloid structural motif by GFP protein family." Proceedings of the National Academy of Sciences 117, no. 36 (August 24, 2020): 22122–27. http://dx.doi.org/10.1073/pnas.2001457117.

Full text

Abstract:

Cnidarian fluorescent protein (FP) derivatives such as GFP, mCherry, and mEOS2 have been widely used to monitor gene expression and protein localization through biological imaging because they are considered functionally inert. We demonstrate that FPs specifically bind amyloid fibrils formed from many natural peptides and proteins. FPs do not bind other nonamyloid fibrillar structures such as microtubules or actin filaments and do not bind to amorphous aggregates. FPs can also bind small aggregates formed during the lag phase and early elongation phase of fibril formation and can inhibit amyloid fibril formation in a dose-dependent manner. These findings suggest caution should be taken in interpreting FP-fusion protein localization data when amyloid structures may be present. Given the pathological significance of amyloid-related species in some diseases, detection and inhibition of amyloid fibril formation using FPs can provide insights on developing diagnostic tools.

APA, Harvard, Vancouver, ISO, and other styles

13

Patil, Sharadrao M., and Andrei T. Alexandrescu. "Charge-Based Inhibitors of Amylin Fibrillization and Toxicity." Journal of Diabetes Research 2015 (2015): 1–13. http://dx.doi.org/10.1155/2015/946037.

Full text

Abstract:

To test the hypothesis that electrostatic repulsion is an important force opposing amyloid fibril assembly, we designed peptides that substitute strings of positively or negatively charged residues into the sequence of the amyloidogenic hormone amylin, which contributes to type 2 diabetes pathology. Arg-1 and Arg-2 substitute four positively charged arginines for segments that in structural models of amylin fibrils form the end of strandβ1 and the beginning of strandβ2, respectively. Mem-T substitutes negatively charged aspartates for the peptide segment with the largest avidity for membranes. All three charge-loaded peptides fibrillize poorly on their own and inhibit fibril elongation of WT-amylin at physiological ionic strength. The inhibition of WT-amylin fibril elongation rates is salt-dependent indicating that the analogs act through electrostatic interactions. Arg-1 protects against WT-amylin cytotoxicity towards a MIN6 mouse model of pancreaticβ-cells, and Arg-2 protects at higher concentrations, whereas Mem-T has no effect. The most effective variant, Arg-1, inhibits WT-amylin fibril elongation rates with an IC50of ~1 µM and cytotoxicity with an IC50of ~50 µM, comparable to other types of fibrillization inhibitors reported in the literature. Taken together, these results suggest that electrostatic interactions can be exploited to develop new types of inhibitors of amyloid fibrillization and toxicity.

APA, Harvard, Vancouver, ISO, and other styles

14

Pepys, M. B. "Pathogenesis, diagnosis and treatment of systemic amyloidosis." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 356, no. 1406 (February 28, 2001): 203–11. http://dx.doi.org/10.1098/rstb.2000.0766.

Full text

Abstract:

Amyloidosis is a disorder of protein folding in which normally soluble proteins are deposited as abnormal, insoluble fibrils that disrupt tissue structure and cause disease. Although about 20 different unrelated proteins can form amyloid fibrils in vivo , all such fibrils share a common cross–β core structure. Some natural wild–type proteins are inherently amyloidogenic, form fibrils and cause amyloidosis in old age or if present for long periods at abnormally high concentration. Other amyloidogenic proteins are acquired or inherited variants, containing amino–acid substitutions that render them unstable so that they populate partly unfolded states under physiological conditions, and these intermediates then aggregate in the stable amyloid fold. In addition to the fibrils, amyloid deposits always contain the non–fibrillar pentraxin plasma protein, serum amyloid P component (SAP), because it undergoes specific calcium–dependent binding to amyloid fibrils. SAP contributes to amyloidogenesis, probably by stabilizing amyloid fibrils and retarding their clearance. Radiolabelled SAP is an extremely useful, safe, specific, non–invasive, quantitative tracer for scintigraphic imaging of systemic amyloid deposits. Its use has demonstrated that elimination of the supply of amyloid fibril precursor proteins leads to regression of amyloid deposits with clinical benefit. Current treatment of amyloidosis comprises careful maintenance of impaired organ function, replacement of end–stage organ failure by dialysis or transplantation, and vigorous efforts to control underlying conditions responsible for production of fibril precursors. New approaches under development include drugs for stabilization of the native fold of precursor proteins, inhibition of fibrillogenesis, reversion of the amyloid to the native fold, and dissociation of SAP to accelerate amyloid fibril clearance in vivo .

APA, Harvard, Vancouver, ISO, and other styles

15

Gupta, Neha, Sameer Quazi, Saurabh Kumar Jha, Mohammad Khursheed Siddiqi, Kanika Verma, Swapnil Sharma, Rizwan Hassan Khan, and Sameer Suresh Bhagyawant. "Chickpea Peptide: A Nutraceutical Molecule Corroborating Neurodegenerative and ACE-I Inhibition." Nutrients 14, no. 22 (November 14, 2022): 4824. http://dx.doi.org/10.3390/nu14224824.

Full text

Abstract:

Chickpea seeds are the source of proteins in human nutrition and attribute some nutraceutical properties. Herein, we report the effects of chickpea seed bioactive peptide on albumin, insulin, lactoglobulin and lysozyme amyloid fibril formation. Employing thioflavin T (ThT) assays and circular dichroism (CD), amyloid structural binding transition was experimented to analyze the inhibition of amyloid fibril formation. The purified active peptide with a molecular mass of 934.53 Da was evaluated in vitro for its ACE-I inhibitory, antibacterial, antifungal and antidiabetic activities. Further, in vivo animal studies were carried out in wistar rats for blood pressure lowering action. In hypertensive rats, chickpea peptide decreased 131 ± 3.57 mm of Hg for systolic blood pressure and 86 ± 1.5 mm of Hg for diastolic blood pressure after 8 h intraperitoneal administration. Additionally, the peptide suppressed the fibrillation of amyloid and destabilized the preformed mature fibrils. Data emphasize efficacy of chickpea peptide vis-a-vis ACE-Inhibitory, antibacterial, antifungal, antidiabetic and anti-amyloidogenic activities, allowing us to propose this novel peptide as a suitable candidate for nutraceutical-based drugs and seems the first kind of its nature.

APA, Harvard, Vancouver, ISO, and other styles

16

Hoepfner, Jeannine, Mandy Kleinsorge, Oliver Papp, Susanne Alfken, Robin Heiringhoff, Andreas Pich, Vanessa Sauer, et al. "In vitro modelling of familial amyloidotic polyneuropathy allows quantitative detection of transthyretin amyloid fibril-like structures in hepatic derivatives of patient-specific induced pluripotent stem cells." Biological Chemistry 398, no. 8 (July 26, 2017): 939–54. http://dx.doi.org/10.1515/hsz-2016-0258.

Full text

Abstract:

Abstract The transthyretin protein is thermodynamically destabilised by mutations in the transthyretin gene, promoting the formation of amyloid fibrils in various tissues. Consequently, impaired autonomic organ function is observed in patients suffering from transthyretin-related familial amyloidotic polyneuropathy (FAP). The influence of individual genetic backgrounds on fibril formation as a potential cause of genotype-phenotype variations needs to be investigated in order to ensure efficient patient-specific therapies. We reprogrammed FAP patient fibroblasts to induced pluripotent stem (iPS) cells and differentiated these cells into transthyretin-expressing hepatocyte-like cells (HLCs). HLCs differentiated from FAP iPS cells and healthy control iPS cells secreted the transthyretin protein in similar concentrations. Mass spectrometry revealed the presence of mutant transthyretin protein in FAP HLC supernatants. In comparison to healthy control iPS cells, we demonstrated the formation of transthyretin amyloid fibril-like structures in FAP HLC supernatants using the amyloid-specific dyes Congo red and thioflavin T. These dyes were also applicable for the quantitative determination of in vitro formed transthyretin fibril-like structures. Moreover, we confirmed the inhibition of fibril formation by the TTR kinetic stabiliser diclofenac. Thioflavin T fluorescence intensity measurements even allowed the quantification of amyloid fibril-like structures in 96-well plate formats as a prerequisite for patient-specific drug screening approaches.

APA, Harvard, Vancouver, ISO, and other styles

17

Palmal, Sharbari, Amit Ranjan Maity, Brijesh Kumar Singh, Sreetama Basu, Nihar R. Jana, and Nikhil R. Jana. "Inhibition of Amyloid Fibril Growth and Dissolution of Amyloid Fibrils by Curcumin-Gold Nanoparticles." Chemistry - A European Journal 20, no. 20 (April 1, 2014): 6184–91. http://dx.doi.org/10.1002/chem.201400079.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

Shvadchak, Volodymyr V., Kseniia Afitska, and Dmytro A. Yushchenko. "Inhibition of α-Synuclein Amyloid Fibril Elongation by Blocking Fibril Ends." Angewandte Chemie 130, no. 20 (April 16, 2018): 5792–96. http://dx.doi.org/10.1002/ange.201801071.

Full text

APA, Harvard, Vancouver, ISO, and other styles

19

Shvadchak, Volodymyr V., Kseniia Afitska, and Dmytro A. Yushchenko. "Inhibition of α-Synuclein Amyloid Fibril Elongation by Blocking Fibril Ends." Angewandte Chemie International Edition 57, no. 20 (April 16, 2018): 5690–94. http://dx.doi.org/10.1002/anie.201801071.

Full text

APA, Harvard, Vancouver, ISO, and other styles

20

Shvadchak, Volodymyr V., Kseniia Afitska, Anna Fucikova, and Dmytro A. Yushchenko. "Inhibition of A-Synuclein Amyloid Fibril Elongation by Blocking Fibril Ends." Biophysical Journal 116, no. 3 (February 2019): 491a. http://dx.doi.org/10.1016/j.bpj.2018.11.2650.

Full text

APA, Harvard, Vancouver, ISO, and other styles

21

Shinde, Meenakshi N., Nilotpal Barooah, Achikanath C. Bhasikuttan, and Jyotirmayee Mohanty. "Inhibition and disintegration of insulin amyloid fibrils: a facile supramolecular strategy with p-sulfonatocalixarenes." Chemical Communications 52, no. 14 (2016): 2992–95. http://dx.doi.org/10.1039/c5cc10159j.

Full text

Abstract:

This study reveals the ability of p-sulfonatocalix[4/6]arenes to effectively inhibit the fibril formation in human insulin and demonstrate its potential to disintegrate/dissolve the mature fibrils, a promising supramolecular therapeutic strategy for amyloidosis.

APA, Harvard, Vancouver, ISO, and other styles

22

Doig, A. J., E. Hughes, R. M. Burke, T. J. Su, R. K. Heenan, and J. Lu. "Inhibition of toxicity and protofibril formation in the amyloid-β peptide β(25–35) using N-Methylated derivatives." Biochemical Society Transactions 30, no. 4 (August 1, 2002): 537–42. http://dx.doi.org/10.1042/bst0300537.

Full text

Abstract:

β(25–35) is a fragment of β-amyloid that retains its wild-type properties. N-methylated derivatives of β(25–35) can block hydrogen bonding on the outer edge of the assembling amyloid, so preventing the aggregation and inhibiting the toxicity of the wild-type peptide. The effects are assayed by Congo Red and thioflavin T binding, electron microscopy and an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] toxicity assay. N-methyl-Gly-25 has similar properties to the wild-type, while five other methylation sites have varying effects on prefolded fibrils and fibril assembly. In particular, N-methyl-Gly-33 is able to completely prevent fibril assembly and reduces the toxicity of prefolded amyloid. With N-methyl-Leu-34 the fibril morphology is altered and toxicity reduced. A preliminary study of β(25–35) structure in aqueous solution was made by small-angle neutron scattering (SANS). The protofibrillar aggregates are best described as a disc of radius 140 å and height 53 å (1 å = 0.1 nm), though the possibility of polydisperse aggregates cannot be ruled out. No aggregates form in the presence of N-methyl-Gly-33. We suggest that the use of N-methylated derivatives of amyloidogenic peptides and proteins could provide a general solution to the problem of amyloid deposition and toxicity and that SANS is an important technique for the direct observation of protofibril formation and destruction in solution.

APA, Harvard, Vancouver, ISO, and other styles

23

Folmert, Kristin, Malgorzata Broncel, Hans v. Berlepsch, Christopher Hans Ullrich, Mary-Ann Siegert, and Beate Koksch. "Inhibition of peptide aggregation by means of enzymatic phosphorylation." Beilstein Journal of Organic Chemistry 12 (November 18, 2016): 2462–70. http://dx.doi.org/10.3762/bjoc.12.240.

Full text

Abstract:

As is the case in numerous natural processes, enzymatic phosphorylation can be used in the laboratory to influence the conformational populations of proteins. In nature, this information is used for signal transduction or energy transfer, but has also been shown to play an important role in many diseases like tauopathies or diabetes. With the goal of determining the effect of phosphorylation on amyloid fibril formation, we designed a model peptide which combines structural characteristics of α-helical coiled-coils and β-sheets in one sequence. This peptide undergoes a conformational transition from soluble structures into insoluble amyloid fibrils over time and under physiological conditions and contains a recognition motif for PKA (cAMP-dependent protein kinase) that enables enzymatic phosphorylation. We have analyzed the pathway of amyloid formation and the influence of enzymatic phosphorylation on the different states along the conformational transition from random-coil to β-sheet-rich oligomers to protofilaments and on to insoluble amyloid fibrils, and we found a remarkable directing effect from β-sheet-rich structures to unfolded structures in the initial growth phase, in which small oligomers and protofilaments prevail if the peptide is phosphorylated.

APA, Harvard, Vancouver, ISO, and other styles

24

Michaels, Thomas C. T., Andela Šarić, Georg Meisl, Gabriella T. Heller, Samo Curk, Paolo Arosio, Sara Linse, Christopher M. Dobson, Michele Vendruscolo, and Tuomas P. J. Knowles. "Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors." Proceedings of the National Academy of Sciences 117, no. 39 (September 14, 2020): 24251–57. http://dx.doi.org/10.1073/pnas.2006684117.

Full text

Abstract:

Understanding the mechanism of action of compounds capable of inhibiting amyloid-fibril formation is critical to the development of potential therapeutics against protein-misfolding diseases. A fundamental challenge for progress is the range of possible target species and the disparate timescales involved, since the aggregating proteins are simultaneously the reactants, products, intermediates, and catalysts of the reaction. It is a complex problem, therefore, to choose the states of the aggregating proteins that should be bound by the compounds to achieve the most potent inhibition. We present here a comprehensive kinetic theory of amyloid-aggregation inhibition that reveals the fundamental thermodynamic and kinetic signatures characterizing effective inhibitors by identifying quantitative relationships between the aggregation and binding rate constants. These results provide general physical laws to guide the design and optimization of inhibitors of amyloid-fibril formation, revealing in particular the important role of on-rates in the binding of the inhibitors.

APA, Harvard, Vancouver, ISO, and other styles

25

Liu, Yanqin, Michael Graetz, Lam Ho, and Tara L. Pukala. "Ion Mobility—Mass Spectrometry-Based Screening for Inhibition of α-Synuclein Aggregation." European Journal of Mass Spectrometry 21, no. 3 (June 2015): 255–64. http://dx.doi.org/10.1255/ejms.1359.

Full text

Abstract:

Aberrant protein folding and formation of amyloid fibrils are associated with numerous debilitating human diseases, for which there are currently no suitable therapeutic treatments. For instance, Parkinson's disease is characterised pathologically by the intraneural accumulation of the amyloid protein α-synuclein. In order to search for new therapeutic agents that are effective in preventing the early conformational changes that precede protein aggregation, it is necessary to devise new analytical screening approaches. Here we demonstrate the use of ion mobility–mass spectrometry for screening of molecules capable of inhibiting the misfolding and aggregation of α-synuclein (specifically, the A53T human mutant). Importantly, this assay allows for the analysis of conformational changes that precede aggregation, and therefore is unique in its ability to identify inhibitors working at the earliest stages of amyloid formation. In addition, we use complementary mass spectrometry methods to probe selected protein–ligand interactions responsible for fibril inhibition.

APA, Harvard, Vancouver, ISO, and other styles

26

JAIKARAN, Emma T. A. S., Melanie R. NILSSON, and Anne CLARK. "Pancreatic beta-cell granule peptides form heteromolecular complexes which inhibit islet amyloid polypeptide fibril formation." Biochemical Journal 377, no. 3 (February 1, 2004): 709–16. http://dx.doi.org/10.1042/bj20030852.

Full text

Abstract:

Islet amyloid polypeptide (IAPP), or ‘amylin’, is co-stored with insulin in secretory granules of pancreatic islet β-cells. In Type 2 diabetes, IAPP converts into a β-sheet conformation and oligomerizes to form amyloid fibrils and islet deposits. Granule components, including insulin, inhibit spontaneous IAPP fibril formation in vitro. To determine the mechanism of this inhibition, molecular interactions of insulin with human IAPP (hIAPP), rat IAPP (rIAPP) and other peptides were examined using surface plasmon resonance (BIAcore), CD and transmission electron microscopy (EM). hIAPP and rIAPP complexed with insulin, and this reaction was concentration-dependent. rIAPP and insulin, but not pro-insulin, bound to hIAPP. Insulin with a truncated B-chain, to prevent dimerization, also bound hIAPP. In the presence of insulin, hIAPP did not spontaneously develop β-sheet secondary structure or form fibrils. Insulin interacted with pre-formed IAPP fibrils in a regular repeating pattern, as demonstrated by immunoEM, suggesting that the binding sites for insulin remain exposed in hIAPP fibrils. Since rIAPP and hIAPP form complexes with insulin (and each other), this could explain the lack of amyloid fibrils in transgenic mice expressing hIAPP. It is likely that IAPP fibrillogenesis is inhibited in secretory granules (where the hIAPP concentration is in the millimolar range) by heteromolecular complex formation with insulin. Alterations in the proportions of insulin and IAPP in granules could disrupt the stability of the peptide. The increase in the proportion of unprocessed pro-insulin produced in Type 2 diabetes could be a major factor in destabilization of hIAPP and induction of fibril formation.

APA, Harvard, Vancouver, ISO, and other styles

27

Obasse, Idira, Mark Taylor, Nigel J. Fullwood, and David Allsop. "Development of proteolytically stable N-methylated peptide inhibitors of aggregation of the amylin peptide implicated in type 2 diabetes." Interface Focus 7, no. 6 (October 20, 2017): 20160127. http://dx.doi.org/10.1098/rsfs.2016.0127.

Full text

Abstract:

Islet amyloid polypeptide, also known as amylin, is the main component of the amyloid deposits present in approximately 90% of people with type 2 diabetes mellitus (T2DM). In this disease, amylin aggregates into multimeric β-pleated sheet structures which cause damage to pancreatic islet β-cells. Inhibitors of early-stage amylin aggregation could therefore provide a disease-modifying treatment for T2DM. In this study, overlapping peptides were designed to target the ‘binding’ region (RLANFLVHSS, residues 11–20) of human amylin, and their effects on amyloid fibril formation were determined by thioflavin-T assay. The first generation peptides showed less than 50% inhibition of aggregation, but a second generation peptide (H 2 N-RGANFLVHGR-CONH 2 ) showed strong inhibitory effects on amylin aggregation, and this was confirmed by negative stain electron microscopy. Cytotoxicity studies revealed that this peptide protected human pancreatic 1.4E7 (ECACC 10070102) insulin-secreting cells from the toxic effects of human amylin. Unlike the retro-inverso version of this peptide, which stimulated aggregation, two N-methylated peptides (H 2 N-RGAmNFmLVmHGR-CONH 2 and H 2 N-RGANmFLmVHmR-CONH 2 ) gave very clear dose-dependent inhibition of fibril formation. These two peptides were also stable against a range of different proteolytic enzymes, and in human plasma. These N-methylated peptides could provide a novel treatment for slowing progression of T2DM.

APA, Harvard, Vancouver, ISO, and other styles

28

Hassan, N., M. L. Cordero, R. Sierpe, M. Almada, J. Juárez, M. Valdez, A. Riveros, et al. "Peptide functionalized magneto-plasmonic nanoparticles obtained by microfluidics for inhibition of β-amyloid aggregation." Journal of Materials Chemistry B 6, no. 31 (2018): 5091–99. http://dx.doi.org/10.1039/c8tb00206a.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Kitagawa, Keisuke, Yohei Misumi, Mitsuharu Ueda, Yuya Hayashi, Masayoshi Tasaki, Konen Obayashi, Taro Yamashita, Hirofumi Jono, Hidetoshi Arima, and Yukio Ando. "Inhibition of insulin amyloid fibril formation by cyclodextrins." Amyloid 22, no. 3 (July 3, 2015): 181–86. http://dx.doi.org/10.3109/13506129.2015.1064818.

Full text

APA, Harvard, Vancouver, ISO, and other styles

30

Martins, Pedro M. "True and apparent inhibition of amyloid fibril formation." Prion 7, no. 2 (March 2013): 136–39. http://dx.doi.org/10.4161/pri.23111.

Full text

APA, Harvard, Vancouver, ISO, and other styles

31

Gazit, Ehud. "Mechanisms of amyloid fibril self-assembly and inhibition." FEBS Journal 272, no. 23 (November 10, 2005): 5971–78. http://dx.doi.org/10.1111/j.1742-4658.2005.05022.x.

Full text

APA, Harvard, Vancouver, ISO, and other styles

32

Pappolla, M., P. Bozner, C. Soto, M. Zagorski, H. Shao, B. Frangione, and J. Ghiso. "Inhibition of Alzheimer's Beta (Aβ) Amyloid Fibril Formation." Emerging Therapeutic Targets 1, no. 1 (January 1997): 77–80. http://dx.doi.org/10.1517/14728222.1.1.77.

Full text

APA, Harvard, Vancouver, ISO, and other styles

33

Scheidt, Tom, Urszula Łapińska, Janet R. Kumita, Daniel R. Whiten, David Klenerman, Mark R. Wilson, Samuel I. A. Cohen, et al. "Secondary nucleation and elongation occur at different sites on Alzheimer’s amyloid-β aggregates." Science Advances 5, no. 4 (April 2019): eaau3112. http://dx.doi.org/10.1126/sciadv.aau3112.

Full text

Abstract:

The aggregates of the Aβ peptide associated with Alzheimer’s disease are able to both grow in size as well as generate, through secondary nucleation, new small oligomeric species, that are major cytotoxins associated with neuronal death. Despite the importance of these amyloid fibril-dependent processes, their structural and molecular underpinnings have remained challenging to elucidate. Here, we consider two molecular chaperones: the Brichos domain, which suppresses specifically secondary nucleation processes, and clusterin which our results show is capable of inhibiting, specifically, the elongation of Aβ fibrils at remarkably low substoichiometric ratios. Microfluidic diffusional sizing measurements demonstrate that this inhibition originates from interactions of clusterin with fibril ends with high affinity. Kinetic experiments in the presence of both molecular chaperones reveal that their inhibitory effects are additive and noncooperative, thereby indicating that the reactive sites associated with the formation of new aggregates and the growth of existing aggregates are distinct.

APA, Harvard, Vancouver, ISO, and other styles

34

Suzuki, Takanobu, Yukiko Hori, Taka Sawazaki, Yusuke Shimizu, Yu Nemoto, Atsuhiko Taniguchi, Shuta Ozawa, Youhei Sohma, Motomu Kanai, and Taisuke Tomita. "Photo-oxygenation inhibits tau amyloid formation." Chemical Communications 55, no. 44 (2019): 6165–68. http://dx.doi.org/10.1039/c9cc01728c.

Full text

APA, Harvard, Vancouver, ISO, and other styles

35

Stańczykiewicz, Bartłomiej, Tomasz M. Goszczyński, Paweł Migdał, Marta Piksa, Krzysztof Pawlik, Jakub Gburek, Krzysztof Gołąb, Bogusława Konopska, and Agnieszka Zabłocka. "Effect of Ovocystatin on Amyloid β 1-42 Aggregation—In Vitro Studies." International Journal of Molecular Sciences 24, no. 6 (March 12, 2023): 5433. http://dx.doi.org/10.3390/ijms24065433.

Full text

Abstract:

Amyloid β peptides (Aβ) aggregating in the brain have a potential neurotoxic effect and are believed to be a major cause of Alzheimer’s disease (AD) development. Thus, inhibiting amyloid polypeptide aggregation seems to be a promising approach to the therapy and prevention of this neurodegenerative disease. The research presented here is directed at the determination of the inhibitory activity of ovocystatin, the cysteine protease inhibitor isolated from egg white, on Aβ42 fibril genesis in vitro. Thioflavin-T (ThT) assays, which determine the degree of aggregation of amyloid peptides based on fluorescence measurement, circular dichroism spectroscopy (CD), and transmission electron microscopy (TEM) have been used to assess the inhibition of amyloid fibril formation by ovocystatin. Amyloid beta 42 oligomer toxicity was measured using the MTT test. The results have shown that ovocystatin possesses Aβ42 anti-aggregation activity and inhibits Aβ42 oligomer toxicity in PC12 cells. The results of this work may help in the development of potential substances able to prevent or delay the process of beta-amyloid aggregation—one of the main reasons for Alzheimer’s disease.

APA, Harvard, Vancouver, ISO, and other styles

36

Ton, Van-Khue, Monica Mukherjee, and Daniel P. Judge. "Transthyretin Cardiac Amyloidosis: Pathogenesis, Treatments, and Emerging Role in Heart Failure with Preserved Ejection Fraction." Clinical Medicine Insights: Cardiology 8s1 (January 2014): CMC.S15719. http://dx.doi.org/10.4137/cmc.s15719.

Full text

Abstract:

Transthyretin (TTR) amyloidosis causes heart failure from cardiac deposition of TTR amyloid fibrils, the by-product of TTR homotetramer disassembly. Wild-type (WT) TTR deposition leads to senile amyloidosis, predominantly manifesting with cardiomyopathy. Missense mutations in the TTR gene result in familial TTR amyloidosis. Certain mutations are more likely to affect the heart, while others cause more neurologic involvement. Extracellular fibril deposition triggers intracellular stress response, upregulation of the inflammatory cascades, apoptosis, and organ dysfunction. Recent studies suggest that TTR cardiac amyloid may be a significant contributor to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Summarized in this review are the molecular pathways underlying the cellular toxicity of TTR amyloid fibrils and the emerging therapies aimed at TTR tetramer stabilization, abrogation of TTR synthesis in the liver, or inhibition of amyloidogenesis.

APA, Harvard, Vancouver, ISO, and other styles

37

Khatua, Deb Kumar, and Mintu Halder. "Distinctively complete inhibition of fibrillation of serum albumins by methotrexate in vitro: experimental and modelling studies to understand the tuning of protein misfolding-related aggregations." New Journal of Chemistry 43, no. 48 (2019): 18983–87. http://dx.doi.org/10.1039/c9nj05128g.

Full text

APA, Harvard, Vancouver, ISO, and other styles

38

Bai, Cuiqin, Dongdong Lin, Yuxiang Mo, Jiangtao Lei, Yunxiang Sun, Luogang Xie, Xinju Yang, and Guanghong Wei. "Influence of fullerenol on hIAPP aggregation: amyloid inhibition and mechanistic aspects." Physical Chemistry Chemical Physics 21, no. 7 (2019): 4022–31. http://dx.doi.org/10.1039/c8cp07501h.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

He, Lei, Xuesong Wang, Dengsen Zhu, Cong Zhao, and Weihong Du. "Methionine oxidation of amyloid peptides by peroxovanadium complexes: inhibition of fibril formation through a distinct mechanism." Metallomics 7, no. 12 (2015): 1562–72. http://dx.doi.org/10.1039/c5mt00133a.

Full text

APA, Harvard, Vancouver, ISO, and other styles

40

Morgan, Gareth J. "Barriers to Small Molecule Drug Discovery for Systemic Amyloidosis." Molecules 26, no. 12 (June 11, 2021): 3571. http://dx.doi.org/10.3390/molecules26123571.

Full text

Abstract:

Inhibition of amyloid fibril formation could benefit patients with systemic amyloidosis. In this group of diseases, deposition of amyloid fibrils derived from normally soluble proteins leads to progressive tissue damage and organ failure. Amyloid formation is a complex process, where several individual steps could be targeted. Several small molecules have been proposed as inhibitors of amyloid formation. However, the exact mechanism of action for a molecule is often not known, which impedes medicinal chemistry efforts to develop more potent molecules. Furthermore, commonly used assays are prone to artifacts that must be controlled for. Here, potential mechanisms by which small molecules could inhibit aggregation of immunoglobulin light-chain dimers, the precursor proteins for amyloid light-chain (AL) amyloidosis, are studied in assays that recapitulate different aspects of amyloidogenesis in vitro. One molecule reduced unfolding-coupled proteolysis of light chains, but no molecules inhibited aggregation of light chains or disrupted pre-formed amyloid fibrils. This work demonstrates the challenges associated with drug development for amyloidosis, but also highlights the potential to combine therapies that target different aspects of amyloidosis.

APA, Harvard, Vancouver, ISO, and other styles

41

Adsi, Hanaa, Shon A. Levkovich, Elvira Haimov, Topaz Kreiser, Massimiliano Meli, Hamutal Engel, Luba Simhaev, et al. "Chemical Chaperones Modulate the Formation of Metabolite Assemblies." International Journal of Molecular Sciences 22, no. 17 (August 25, 2021): 9172. http://dx.doi.org/10.3390/ijms22179172.

Full text

Abstract:

The formation of amyloid-like structures by metabolites is associated with several inborn errors of metabolism (IEMs). These structures display most of the biological, chemical and physical properties of protein amyloids. However, the molecular interactions underlying the assembly remain elusive, and so far, no modulating therapeutic agents are available for clinical use. Chemical chaperones are known to inhibit protein and peptide amyloid formation and stabilize misfolded enzymes. Here, we provide an in-depth characterization of the inhibitory effect of osmolytes and hydrophobic chemical chaperones on metabolite assemblies, thus extending their functional repertoire. We applied a combined in vivo-in vitro-in silico approach and show their ability to inhibit metabolite amyloid-induced toxicity and reduce cellular amyloid content in yeast. We further used various biophysical techniques demonstrating direct inhibition of adenine self-assembly and alteration of fibril morphology by chemical chaperones. Using a scaffold-based approach, we analyzed the physiochemical properties of various dimethyl sulfoxide derivatives and their role in inhibiting metabolite self-assembly. Lastly, we employed whole-atom molecular dynamics simulations to elucidate the role of hydrogen bonds in osmolyte inhibition. Our results imply a dual mode of action of chemical chaperones as IEMs therapeutics, that could be implemented in the rational design of novel lead-like molecules.

APA, Harvard, Vancouver, ISO, and other styles

42

Ban, Tadato, Masaru Hoshino, Satoshi Takahashi, Daizo Hamada, Kazuhiro Hasegawa, Hironobu Naiki, and Yuji Goto. "Direct Observation of Aβ Amyloid Fibril Growth and Inhibition." Journal of Molecular Biology 344, no. 3 (November 2004): 757–67. http://dx.doi.org/10.1016/j.jmb.2004.09.078.

Full text

APA, Harvard, Vancouver, ISO, and other styles

43

Zhang, Wenjie, Andrew J. Christofferson, Quinn A. Besford, Joseph J. Richardson, Junling Guo, Yi Ju, Kristian Kempe, Irene Yarovsky, and Frank Caruso. "Metal-dependent inhibition of amyloid fibril formation: synergistic effects of cobalt–tannic acid networks." Nanoscale 11, no. 4 (2019): 1921–28. http://dx.doi.org/10.1039/c8nr09221d.

Full text

APA, Harvard, Vancouver, ISO, and other styles

44

Tavanti, Francesco, Alfonso Pedone, and Maria Cristina Menziani. "Insights into the Effect of Curcumin and (–)-Epigallocatechin-3-Gallate on the Aggregation of Aβ(1–40) Monomers by Means of Molecular Dynamics." International Journal of Molecular Sciences 21, no. 15 (July 30, 2020): 5462. http://dx.doi.org/10.3390/ijms21155462.

Full text

Abstract:

In this study, we compared the effects of two well-known natural compounds on the early step of the fibrillation process of amyloid-β (1–40), responsible for the formation of plaques in the brains of patients affected by Alzheimer’s disease (AD). The use of extensive replica exchange simulations up to the µs scale allowed us to characterize the inhibition activity of (–)-epigallocatechin-3-gallate (EGCG) and curcumin (CUR) on unfolded amyloid fibrils. A reduced number of β-strands, characteristic of amyloid fibrils, and an increased distance between the amino acids that are responsible for the intra- and interprotein aggregations are observed. The central core region of the amyloid-β (Aβ(1–40)) fibril is found to have a high affinity to EGCG and CUR due to the presence of hydrophobic residues. Lastly, the free binding energy computed using the Poisson Boltzmann Surface Ares suggests that EGCG is more likely to bind to unfolded Aβ(1–40) fibrils and that this molecule can be a good candidate to develop new and more effective congeners to treat AD.

APA, Harvard, Vancouver, ISO, and other styles

45

Wang, Steven S. S., Ya-Ting Chen, and Shang-Wei Chou. "Inhibition of amyloid fibril formation of β-amyloid peptides via the amphiphilic surfactants." Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1741, no. 3 (September 2005): 307–13. http://dx.doi.org/10.1016/j.bbadis.2005.05.004.

Full text

APA, Harvard, Vancouver, ISO, and other styles

46

Sharafdini, Raziyeh, and Hamid Mosaddeghi. "Inhibition of Insulin Amyloid Fibrillation by Salvianolic Acids and Calix[n]arenes: Molecular Docking Insight." Journal of Computational Biophysics and Chemistry 20, no. 05 (August 2021): 539–55. http://dx.doi.org/10.1142/s2737416521500332.

Full text

Abstract:

In this study, the ability of salvianolic acids A, B, C, F, G and calix[[Formula: see text]]arenes ([Formula: see text], 5, 6 and 8) with different upper rims in the inhibition of insulin amyloid fibril formation was studied using molecular docking. The results were analyzed from a molecular point of view. All of the considering ligands interacted with significant residues of insulin, which had a crucial role in the process of insulin fibrillation. The interactions among the ligands and insulin residues could be done through hydrogen bonding and hydrophobic interactions with good binding affinity. So, these ligands could prevent the formation of the insulin fibril. The good consistency of the docking results of [Formula: see text]-sulfonatocalix[4]arene and [Formula: see text]-sulfonatocalix[6]arene with the experimental results in the previous literature represented the capacity of the current theoretical method to supplement and interpret experimental findings. Also, in this study, salvianolic acids A, C, F and G were suggested as new inhibitors of the insulin amyloid fibril.

APA, Harvard, Vancouver, ISO, and other styles

47

ZHANG, Bao-Hong, Guo-Sheng HU, Deng-Sen ZHU, Wen-Ji WANG, Ge-Hui GONG, and Wei-Hong DU. "Inhibition of Prion Amyloid Peptide Fibril Formation by Peroxovanadium Complexes." Acta Physico-Chimica Sinica 32, no. 7 (2016): 1810–18. http://dx.doi.org/10.3866/pku.whxb201604145.

Full text

APA, Harvard, Vancouver, ISO, and other styles

48

Todorova, Nevena, Levi Yeung, Andrew Hung, and Irene Yarovsky. ""Janus" Cyclic Peptides: A New Approach to Amyloid Fibril Inhibition?" PLoS ONE 8, no. 2 (February 20, 2013): e57437. http://dx.doi.org/10.1371/journal.pone.0057437.

Full text

APA, Harvard, Vancouver, ISO, and other styles

49

Ozawa, Daisaku, Kazuhiro Hasegawa, Young-Ho Lee, Kazumasa Sakurai, Kotaro Yanagi, Tadakazu Ookoshi, Yuji Goto, and Hironobu Naiki. "Inhibition of β2-Microglobulin Amyloid Fibril Formation by α2-Macroglobulin." Journal of Biological Chemistry 286, no. 11 (January 7, 2011): 9668–76. http://dx.doi.org/10.1074/jbc.m110.167965.

Full text

APA, Harvard, Vancouver, ISO, and other styles

50

Cohen, Tomer, Anat Frydman-Marom, Meirav Rechter, and Ehud Gazit. "Inhibition of Amyloid Fibril Formation and Cytotoxicity by Hydroxyindole Derivatives†." Biochemistry 45, no. 15 (April 2006): 4727–35. http://dx.doi.org/10.1021/bi051525c.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Amyloid Fibril Inhibition'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles