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Journal articles on the topic 'Preformed fibrils'

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Author: Grafiati

Published: 10 December 2022

Last updated: 28 January 2023

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1

Ogawa, Kenjirou, Ayumi Ishii, Aimi Shindo, Kunihiro Hongo, Tomohiro Mizobata, Tetsuya Sogon, and Yasushi Kawata. "Spearmint Extract Containing Rosmarinic Acid Suppresses Amyloid Fibril Formation of Proteins Associated with Dementia." Nutrients 12, no. 11 (November 13, 2020): 3480. http://dx.doi.org/10.3390/nu12113480.

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Neurological dementias such as Alzheimer’s disease and Lewy body dementia are thought to be caused in part by the formation and deposition of characteristic insoluble fibrils of polypeptides such as amyloid beta (Aβ), Tau, and/or α-synuclein (αSyn). In this context, it is critical to suppress and remove such aggregates in order to prevent and/or delay the progression of dementia in these ailments. In this report, we investigated the effects of spearmint extract (SME) and rosmarinic acid (RA; the major component of SME) on the amyloid fibril formation reactions of αSyn, Aβ, and Tau proteins in vitro. SME or RA was added to soluble samples of each protein and the formation of fibrils was monitored by thioflavin T (ThioT) binding assays and transmission electron microscopy (TEM). We also evaluated whether preformed amyloid fibrils could be dissolved by the addition of RA. Our results reveal for the first time that SME and RA both suppress amyloid fibril formation, and that RA could disassemble preformed fibrils of αSyn, Aβ, and Tau into non-toxic species. Our results suggest that SME and RA may potentially suppress amyloid fibrils implicated in the progression of Alzheimer’s disease and Lewy body dementia in vivo, as well.

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Karunarathne, Kanchana, Nabila Bushra, Olivia Williams, Imad Raza, Laura Tirado, Diane Fakhre, Fadia Fakhre, and Martin Muschol. "Self-Assembly of Amyloid Fibrils Into 3D Gel Clusters Versus 2D Sheets." Biomolecules 13, no. 2 (January 24, 2023): 230. http://dx.doi.org/10.3390/biom13020230.

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The deposition of dense fibril plaques represents the pathological hallmark for a multitude of human disorders, including many neurodegenerative diseases. Fibril plaques are predominately composed of amyloid fibrils, characterized by their underlying cross beta-sheet architecture. Research into the mechanisms of amyloid formation has mostly focused on characterizing and modeling the growth of individual fibrils and associated oligomers from their monomeric precursors. Much less is known about the mechanisms causing individual fibrils to assemble into ordered fibrillar suprastructures. Elucidating the mechanisms regulating this “secondary” self-assembly into distinct suprastructures is important for understanding how individual protein fibrils form the prominent macroscopic plaques observed in disease. Whether and how amyloid fibrils assemble into either 2D or 3D supramolecular structures also relates to ongoing efforts on using amyloid fibrils as substrates or scaffolds for self-assembling functional biomaterials. Here, we investigated the conditions under which preformed amyloid fibrils of a lysozyme assemble into larger superstructures as a function of charge screening or pH. Fibrils either assembled into three-dimensional gel clusters or two-dimensional fibril sheets. The latter displayed optical birefringence, diagnostic of amyloid plaques. We presume that pH and salt modulate fibril charge repulsion, which allows anisotropic fibril–fibril attraction to emerge and drive the transition from 3D to 2D fibril self-assembly.

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3

Ferreira, Elisabete, Zaida L. Almeida, Pedro F. Cruz, Marta Silva e Sousa, Paula Veríssimo, and Rui M. M. Brito. "Searching for the Best Transthyretin Aggregation Protocol to Study Amyloid Fibril Disruption." International Journal of Molecular Sciences 23, no. 1 (December 30, 2021): 391. http://dx.doi.org/10.3390/ijms23010391.

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Several degenerative amyloid diseases, with no fully effective treatment, affect millions of people worldwide. These pathologies—amyloidoses—are known to be associated with the formation of ordered protein aggregates and highly stable and insoluble amyloid fibrils, which are deposited in multiple tissues and organs. The disruption of preformed amyloid aggregates and fibrils is one possible therapeutic strategy against amyloidosis; however, only a few compounds have been identified as possible fibril disruptors in vivo to date. To properly identify chemical compounds as potential fibril disruptors, a reliable, fast, and economic screening protocol must be developed. For this purpose, three amyloid fibril formation protocols using transthyretin (TTR), a plasma protein involved in several amyloidoses, were studied using thioflavin-T fluorescence assays, circular dichroism (CD), turbidity, dynamic light scattering (DLS), and transmission electron microscopy (TEM), in order to characterize and select the most appropriate fibril formation protocol. Saturation transfer difference nuclear magnetic resonance spectroscopy (STD NMR) was successfully used to study the interaction of doxycycline, a known amyloid fibril disruptor, with preformed wild-type TTR (TTRwt) aggregates and fibrils. DLS and TEM were also used to characterize the effect of doxycycline on TTRwt amyloid species disaggregation. A comparison of the TTR amyloid morphology formed in different experimental conditions is also presented.

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4

Musteikyte, Greta, Mantas Ziaunys, and Vytautas Smirnovas. "Methylene blue inhibits nucleation and elongation of SOD1 amyloid fibrils." PeerJ 8 (August 14, 2020): e9719. http://dx.doi.org/10.7717/peerj.9719.

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Protein aggregation into highly-structured amyloid fibrils is linked to several neurodegenerative diseases. Such fibril formation by superoxide dismutase I (SOD1) is considered to be related to amyotrophic lateral sclerosis, a late-onset and fatal disorder. Despite much effort and the discovery of numerous anti-amyloid compounds, no effective cure or treatment is currently available. Methylene blue (MB), a phenothiazine dye, has been shown to modulate the aggregation of multiple amyloidogenic proteins. In this work we show its ability to inhibit both the spontaneous amyloid aggregation of SOD1 as well as elongation of preformed fibrils.

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5

Yang, Yaqi, Shiwu Li, Qin Zhang, Ying Kuang, Anjun Qin, Meng Gao, Feng Li, and Ben Zhong Tang. "An AIE-active theranostic probe for light-up detection of Aβ aggregates and protection of neuronal cells." Journal of Materials Chemistry B 7, no. 15 (2019): 2434–41. http://dx.doi.org/10.1039/c9tb00121b.

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An AIE-active probe of Cur-N-BF₂ is developed for light-up detection of Aβ fibrils and plaques, inhibition of Aβ fibrillation, disassembly of preformed Aβ fibrils, and protection of neuronal cells.

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6

Tabassum, Shatera, Abdullah Md Sheikh, Shozo Yano, Takahisa Ikeue, Shingo Mitaki, Makoto Michikawa, and Atsushi Nagai. "A Cationic Gallium Phthalocyanine Inhibits Amyloid β Peptide Fibril Formation." Current Alzheimer Research 17, no. 7 (November 16, 2020): 589–600. http://dx.doi.org/10.2174/1567205017666201008112002.

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Background: Amyloid β (Aβ) peptide deposition is considered as the main cause of Alzheimer’s disease (AD). Previously, we have shown that a Zn containing neutral phthalocyanine (Zn-Pc) inhibits Aβ fibril formation. Objective: The objective of this study is to investigate the effects of a cationic gallium containing Pc (GaCl-Pc) on Aβ fibril formation process. Methods and Results: Aβ fibril formation was induced by incubating synthetic Aβ peptides in a fibril forming buffer, and the amount of fibril was evaluated by ThT fluorescence assay. GaCl-Pc dosedependently inhibited both Aβ1-40 and Aβ1-42 fibril formation. It mainly inhibited the elongation phase of Aβ1-42 fibril formation kinetics, but not the lag phase. Western blotting results showed that it did not inhibit its oligomerization process, rather increased it. Additionally, GaCl-Pc destabilized preformed Aβ1- 42 fibrils dose-dependently in vitro condition, and decreased Aβ levels in the brain slice culture of APP transgenic AD model mice (J20 strain). Near-infrared scanning results showed that GaCl-Pc had the ability to bind to Aβ1-42. MTT assay demonstrated that GaCl-Pc did not have toxicity towards a neuronal cell line (A1) in culture rather, showed protective effects on Aβ-induced toxicity. Moreover, it dosedependently decreased Aβ-induced reactive oxygen species levels in A1 culture. Conclusion: Thus, our result demonstrated that GaCl-Pc decreased Aβ aggregation and destabilized the preformed fibrils. Since cationic molecules show a better ability to cross the blood-brain barrier, cationic GaCl-Pc could be important for the therapy of AD.

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7

Almeida, Zaida L., and Rui M. M. Brito. "Amyloid Disassembly: What Can We Learn from Chaperones?" Biomedicines 10, no. 12 (December 17, 2022): 3276. http://dx.doi.org/10.3390/biomedicines10123276.

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Protein aggregation and subsequent accumulation of insoluble amyloid fibrils with cross-β structure is an intrinsic characteristic of amyloid diseases, i.e., amyloidoses. Amyloid formation involves a series of on-pathway and off-pathway protein aggregation events, leading to mature insoluble fibrils that eventually accumulate in multiple tissues. In this cascade of events, soluble oligomeric species are formed, which are among the most cytotoxic molecular entities along the amyloid cascade. The direct or indirect action of these amyloid soluble oligomers and amyloid protofibrils and fibrils in several tissues and organs lead to cell death in some cases and organ disfunction in general. There are dozens of different proteins and peptides causing multiple amyloid pathologies, chief among them Alzheimer’s, Parkinson’s, Huntington’s, and several other neurodegenerative diseases. Amyloid fibril disassembly is among the disease-modifying therapeutic strategies being pursued to overcome amyloid pathologies. The clearance of preformed amyloids and consequently the arresting of the progression of organ deterioration may increase patient survival and quality of life. In this review, we compiled from the literature many examples of chemical and biochemical agents able to disaggregate preformed amyloids, which have been classified as molecular chaperones, chemical chaperones, and pharmacological chaperones. We focused on their mode of action, chemical structure, interactions with the fibrillar structures, morphology and toxicity of the disaggregation products, and the potential use of disaggregation agents as a treatment option in amyloidosis.

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8

Paul, Ashim, Wen-Hao Li, Guru KrishnaKumar Viswanathan, Elad Arad, Satabdee Mohapatra, Gao Li, Raz Jelinek, Ehud Gazit, Yan-Mei Li, and Daniel Segal. "Tryptophan–glucosamine conjugates modulate tau-derived PHF6 aggregation at low concentrations." Chemical Communications 55, no. 97 (2019): 14621–24. http://dx.doi.org/10.1039/c9cc06868f.

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9

Jha, Anjali, Vandana Ghormade, Henry Kolge, and Kishore M. Paknikar. "Dual effect of chitosan-based nanoparticles on the inhibition of β-amyloid peptide aggregation and disintegration of the preformed fibrils." Journal of Materials Chemistry B 7, no. 21 (2019): 3362–73. http://dx.doi.org/10.1039/c9tb00162j.

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10

Maity, Debabrata, Sunil Kumar, Ruyof AlHussein, Lothar Gremer, Madeline Howarth, Laura Karpauskaite, Wolfgang Hoyer, Mazin Magzoub, and Andrew D. Hamilton. "Sub-stoichiometric inhibition of IAPP aggregation: a peptidomimetic approach to anti-amyloid agents." RSC Chemical Biology 1, no. 4 (2020): 225–32. http://dx.doi.org/10.1039/d0cb00086h.

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Naphthalimide-appended oligopyridylamide peptidomimetic modulate islet amyloid polypeptide amyloidogenesis and disaggregate preformed oligomers and fibrils into non-toxic conformations at substoichiometric concentration.

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11

Tipping, Kevin W., Theodoros K. Karamanos, Toral Jakhria, Matthew G. Iadanza, Sophia C. Goodchild, Roman Tuma, Neil A. Ranson, Eric W. Hewitt, and Sheena E. Radford. "pH-induced molecular shedding drives the formation of amyloid fibril-derived oligomers." Proceedings of the National Academy of Sciences 112, no. 18 (April 20, 2015): 5691–96. http://dx.doi.org/10.1073/pnas.1423174112.

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Amyloid disorders cause debilitating illnesses through the formation of toxic protein aggregates. The mechanisms of amyloid toxicity and the nature of species responsible for mediating cellular dysfunction remain unclear. Here, using β2-microglobulin (β2m) as a model system, we show that the disruption of membranes by amyloid fibrils is caused by the molecular shedding of membrane-active oligomers in a process that is dependent on pH. Using thioflavin T (ThT) fluorescence, NMR, EM and fluorescence correlation spectroscopy (FCS), we show that fibril disassembly at pH 6.4 results in the formation of nonnative spherical oligomers that disrupt synthetic membranes. By contrast, fibril dissociation at pH 7.4 results in the formation of nontoxic, native monomers. Chemical cross-linking or interaction with hsp70 increases the kinetic stability of fibrils and decreases their capacity to cause membrane disruption and cellular dysfunction. The results demonstrate how pH can modulate the deleterious effects of preformed amyloid aggregates and suggest why endocytic trafficking through acidic compartments may be a key factor in amyloid disease.

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12

Patrias, Lynnae M., Andrea C. Klaver, Mary P. Coffey, John M. Finke, Jyothi L. Digambaranath, Loan Dang, Alvaro A. Martinez, and David A. Loeffler. "Effects of External Beam Radiation onIn VitroFormation of Abeta1-42 Fibrils and Preformed Fibrils." Radiation Research 175, no. 3 (March 2011): 375–81. http://dx.doi.org/10.1667/rr2448.1.

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13

Kim, Kyoungdo, Kwang-su Park, Mi Kyoung Kim, Hyunah Choo, and Youhoon Chong. "Dicyanovinyl-substituted J147 analogue inhibits oligomerization and fibrillation of β-amyloid peptides and protects neuronal cells from β-amyloid-induced cytotoxicity." Organic & Biomolecular Chemistry 13, no. 37 (2015): 9564–69. http://dx.doi.org/10.1039/c5ob01463h.

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14

Ono, Kenjiro, Mie Hirohata, and Masahito Yamada. "Ferulic acid destabilizes preformed β-amyloid fibrils in vitro." Biochemical and Biophysical Research Communications 336, no. 2 (October 2005): 444–49. http://dx.doi.org/10.1016/j.bbrc.2005.08.148.

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15

Ren, Baiping, Yonglan Liu, Yanxian Zhang, Mingzhen Zhang, Yan Sun, Guizhao Liang, Jianxiong Xu, and Jie Zheng. "Tanshinones inhibit hIAPP aggregation, disaggregate preformed hIAPP fibrils, and protect cultured cells." Journal of Materials Chemistry B 6, no. 1 (2018): 56–67. http://dx.doi.org/10.1039/c7tb02538f.

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16

Guo, Min, Jian Wang, Yanxin Zhao, Yiwei Feng, Sida Han, Qiang Dong, Mei Cui, and Kim Tieu. "Microglial exosomes facilitate α-synuclein transmission in Parkinson’s disease." Brain 143, no. 5 (May 1, 2020): 1476–97. http://dx.doi.org/10.1093/brain/awaa090.

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Abstract Accumulation of neuronal α-synuclein is a prominent feature in Parkinson’s disease. More recently, such abnormal protein aggregation has been reported to spread from cell to cell and exosomes are considered as important mediators. The focus of such research, however, has been primarily in neurons. Given the increasing recognition of the importance of non-cell autonomous-mediated neurotoxicity, it is critical to investigate the contribution of glia to α-synuclein aggregation and spread. Microglia are the primary phagocytes in the brain and have been well-documented as inducers of neuroinflammation. How and to what extent microglia and their exosomes impact α-synuclein pathology has not been well delineated. We report here that when treated with human α-synuclein preformed fibrils, exosomes containing α-synuclein released by microglia are fully capable of inducing protein aggregation in the recipient neurons. Additionally, when combined with microglial proinflammatory cytokines, these exosomes further increased protein aggregation in neurons. Inhibition of exosome synthesis in microglia reduced α-synuclein transmission. The in vivo significance of these exosomes was demonstrated by stereotaxic injection of exosomes isolated from α-synuclein preformed fibrils treated microglia into the mouse striatum. Phosphorylated α-synuclein was observed in multiple brain regions consistent with their neuronal connectivity. These animals also exhibited neurodegeneration in the nigrostriatal pathway in a time-dependent manner. Depleting microglia in vivo dramatically suppressed the transmission of α-synuclein after stereotaxic injection of preformed fibrils. Mechanistically, we report here that α-synuclein preformed fibrils impaired autophagy flux by upregulating PELI1, which in turn, resulted in degradation of LAMP2 in activated microglia. More importantly, by purifying microglia/macrophage derived exosomes in the CSF of Parkinson’s disease patients, we confirmed the presence of α-synuclein oligomer in CD11b+ exosomes, which were able to induce α-synuclein aggregation in neurons, further supporting the translational aspect of this study. Taken together, our study supports the view that microglial exosomes contribute to the progression of α-synuclein pathology and therefore, they may serve as a promising therapeutic target for Parkinson’s disease.

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17

Ono, Kenjiro, Kazuhiro Hasegawa, Masahito Yamada, and Hironobu Naiki. "Nicotine breaks down preformed Alzheimer’s β-amyloid fibrils in vitro." Biological Psychiatry 52, no. 9 (November 2002): 880–86. http://dx.doi.org/10.1016/s0006-3223(02)01417-8.

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18

Pandey, Nitin Kumar, Sudeshna Ghosh, and Swagata Dasgupta. "Effect of surfactants on preformed fibrils of human serum albumin." International Journal of Biological Macromolecules 59 (August 2013): 39–45. http://dx.doi.org/10.1016/j.ijbiomac.2013.04.014.

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19

Sood, Abha, Mohammed Abid, Catharine Sauer, Samson Hailemichael, Michelle Foster, Béla Török, and Marianna Török. "Disassembly of preformed amyloid beta fibrils by small organofluorine molecules." Bioorganic & Medicinal Chemistry Letters 21, no. 7 (April 2011): 2044–47. http://dx.doi.org/10.1016/j.bmcl.2011.02.012.

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20

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.

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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.

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21

Verma, Dinesh Kumar, Bo Am Seo, Anurupa Ghosh, Shi-Xun Ma, Karina Hernandez-Quijada, Julie K. Andersen, Han Seok Ko, and Yong-Hwan Kim. "Alpha-Synuclein Preformed Fibrils Induce Cellular Senescence in Parkinson’s Disease Models." Cells 10, no. 7 (July 5, 2021): 1694. http://dx.doi.org/10.3390/cells10071694.

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Emerging evidence indicates that cellular senescence could be a critical inducing factor for aging-associated neurodegenerative disorders. However, the involvement of cellular senescence remains unclear in Parkinson’s disease (PD). To determine this, we assessed the effects of α-synuclein preformed fibrils (α-syn PFF) or 1-methyl-4-phenylpyridinium (MPP+) on changes in cellular senescence markers, employing α-syn PFF treated-dopaminergic N27 cells, primary cortical neurons, astrocytes and microglia and α-syn PFF-injected mouse brain tissues, as well as human PD patient brains. Our results demonstrate that α-syn PFF-induced toxicity reduces the levels of Lamin B1 and HMGB1, both established markers of cellular senescence, in correlation with an increase in the levels of p21, a cell cycle-arrester and senescence marker, in both reactive astrocytes and microglia in mouse brains. Using Western blot and immunohistochemistry, we found these cellular senescence markers in reactive astrocytes as indicated by enlarged cell bodies within GFAP-positive cells and Iba1-positive activated microglia in α-syn PFF injected mouse brains. These results indicate that PFF-induced pathology could lead to astrocyte and/or microglia senescence in PD brains, which may contribute to neuropathology in this model. Targeting senescent cells using senolytics could therefore constitute a viable therapeutic option for the treatment of PD.

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22

Wang, Jian-Bo, Yi-Min Wang, and Cheng-Ming Zeng. "Quercetin inhibits amyloid fibrillation of bovine insulin and destabilizes preformed fibrils." Biochemical and Biophysical Research Communications 415, no. 4 (December 2011): 675–79. http://dx.doi.org/10.1016/j.bbrc.2011.10.135.

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23

Ono, Kenjiro, Kazuhiro Hasegawa, Hironobu Naiki, and Masahito Yamada. "Preformed β-amyloid fibrils are destabilized by coenzyme Q10 in vitro." Biochemical and Biophysical Research Communications 330, no. 1 (April 2005): 111–16. http://dx.doi.org/10.1016/j.bbrc.2005.02.132.

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24

Durairajan, Siva Sundara Kumar, Qiuju Yuan, Lixia Xie, Wing-Sai Chan, Wan-Fung Kum, Irene Koo, Chenli Liu, et al. "Salvianolic acid B inhibits Aβ fibril formation and disaggregates preformed fibrils and protects against Aβ-induced cytotoxicty." Neurochemistry International 52, no. 4-5 (March 2008): 741–50. http://dx.doi.org/10.1016/j.neuint.2007.09.006.

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25

Andrade, Stéphanie, Joana A. Loureiro, and Maria C. Pereira. "Transferrin-Functionalized Liposomes for the Delivery of Gallic Acid: A Therapeutic Approach for Alzheimer’s Disease." Pharmaceutics 14, no. 10 (October 11, 2022): 2163. http://dx.doi.org/10.3390/pharmaceutics14102163.

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Senile plaques composed of amyloid β (Aβ) fibrils are considered the leading cause of Alzheimer’s disease (AD). Molecules with the ability to inhibit Aβ aggregation and/or promote Aβ clearance are thus a promising approach for AD therapy. Our group recently demonstrated that gallic acid (GA) has strong anti-amyloidogenic properties. In this study, stealth liposomes were prepared for the delivery of GA for AD therapy. The liposomes were functionalized with transferrin (Tf) to direct them to the brain, since Tf receptors are overexpressed in the endothelial cells of the blood–brain barrier. GA-loaded Tf-functionalized liposomes showed mean diameters of 130 nm, low polydispersity index values, and neutral zeta potential. Moreover, the produced nanocarriers promoted the sustained release of GA over 5 days and are physically stable for 1 month under storage conditions. Furthermore, GA-loaded Tf-functionalized liposomes showed a strong ability to interact with Aβ1-42 monomers, slowing down the Aβ monomer-to-oligomer and oligomer-to-fibril transitions and decreasing the number of fibrils formed by 56%. In addition, the NPs disaggregated approximately 30% of preformed Aβ fibrils. The presented results suggest that Tf-functionalized liposomes could be a viable platform for the brain delivery of GA for AD therapy. Studies with animal models of AD will be valuable for validating the therapeutic efficacy of this novel liposomal formulation.

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Liu, Fufeng, Fang Zhao, Wenjuan Wang, Jingcheng Sang, Longgang Jia, Li Li, and Fuping Lu. "Cyanidin-3-O-glucoside inhibits Aβ40 fibrillogenesis, disintegrates preformed fibrils, and reduces amyloid cytotoxicity." Food & Function 11, no. 3 (2020): 2573–87. http://dx.doi.org/10.1039/c9fo00316a.

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Cyanidin-3-O-glucoside, a common anthocyanin, is a potential functional inhibitor to ameliorate Alzheimer's disease by inhibiting Aβ fibrillogenesis, disrupting the mature Aβ fibrils, and reducing amyloid-induced cytotoxicity.

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Raman, Bakthisaran, Tadato Ban, Kei-ichi Yamaguchi, Miyo Sakai, Tomoji Kawai, Hironobu Naiki, and Yuji Goto. "Metal Ion-dependent Effects of Clioquinol on the Fibril Growth of an Amyloid β Peptide." Journal of Biological Chemistry 280, no. 16 (February 16, 2005): 16157–62. http://dx.doi.org/10.1074/jbc.m500309200.

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Although metal ions such as Cu2+, Zn2+, and Fe3+are implicated to play a key role in Alzheimer disease, their role is rather complex, and comprehensive understanding is not yet obtained. We show that Cu2+and Zn2+but not Fe3+renders the amyloid β peptide, Aβ1–40, nonfibrillogenic in nature. However, preformed fibrils of Aβ1–40were stable when treated with these metal ions. Consequently, fibril growth of Aβ1–40could be switched on/off by switching the molecule between its apo- and holo-forms. Clioquinol, a potential drug for Alzheimer disease, induced resumption of the Cu2+-suppressed but not the Zn2+-suppressed fibril growth of Aβ1–40. The observed synergistic effect of clioquinol and Zn2+suggests that Zn2+-clioquinol complex effectively retards fibril growth. Thus, clioquinol has dual effects; although it disaggregates the metal ion-induced aggregates of Aβ1–40through metal chelation, it further retards the fibril growth along with Zn2+. These results indicate the mechanism of metal ions in suppressing Aβ amyloid formation, as well as providing information toward the use of metal ion chelators, particularly clioquinol, as potential drugs for Alzheimer disease.

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Werner, Tony E. R., David Bernson, Elin K. Esbjörner, Sandra Rocha, and Pernilla Wittung-Stafshede. "Amyloid formation of fish β-parvalbumin involves primary nucleation triggered by disulfide-bridged protein dimers." Proceedings of the National Academy of Sciences 117, no. 45 (October 22, 2020): 27997–8004. http://dx.doi.org/10.1073/pnas.2015503117.

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Amyloid formation involves the conversion of soluble protein species to an aggregated state. Amyloid fibrils of β-parvalbumin, a protein abundant in fish, act as an allergen but also inhibit the in vitro assembly of the Parkinson protein α-synuclein. However, the intrinsic aggregation mechanism of β-parvalbumin has not yet been elucidated. We performed biophysical experiments in combination with mathematical modeling of aggregation kinetics and discovered that the aggregation of β-parvalbumin is initiated by the formation of dimers stabilized by disulfide bonds and then proceeds via primary nucleation and fibril elongation processes. Dimer formation is accelerated by H2O2and hindered by reducing agents, resulting in faster and slower aggregation rates, respectively. Purified β-parvalbumin dimers readily assemble into amyloid fibrils with similar morphology as those formed when starting from monomer solutions. Furthermore, addition of preformed dimers accelerates the aggregation reaction of monomers. Aggregation of purified β-parvalbumin dimers follows the same kinetic mechanism as that of monomers, implying that the rate-limiting primary nucleus is larger than a dimer and/or involves structural conversion. Our findings demonstrate a folded protein system in which spontaneously formed intermolecular disulfide bonds initiate amyloid fibril formation by recruitment of monomers. This dimer-induced aggregation mechanism may be of relevance for human amyloid diseases in which oxidative stress is often an associated hallmark.

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Choi, Erika Y., Sam Sik Kang, Sang Kook Lee, and Byung Hee Han. "Polyphenolic Biflavonoids Inhibit Amyloid-Beta Fibrillation and Disaggregate Preformed Amyloid-Beta Fibrils." Biomolecules & Therapeutics 28, no. 2 (March 1, 2020): 145–51. http://dx.doi.org/10.4062/biomolther.2019.113.

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30

Zhang, Qiang, Hisham Abdelmotilib, Travis Larson, Cameron Keomanivong, Mackenzie Conlon, Georgina M. Aldridge, and Nandakumar S. Narayanan. "Cortical alpha-synuclein preformed fibrils do not affect interval timing in mice." Neuroscience Letters 765 (November 2021): 136273. http://dx.doi.org/10.1016/j.neulet.2021.136273.

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31

Bunce, Samuel J., Yiming Wang, Katie L. Stewart, Alison E. Ashcroft, Sheena E. Radford, Carol K. Hall, and Andrew J. Wilson. "Molecular insights into the surface-catalyzed secondary nucleation of amyloid-β40 (Aβ40) by the peptide fragment Aβ16–22." Science Advances 5, no. 6 (June 2019): eaav8216. http://dx.doi.org/10.1126/sciadv.aav8216.

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Understanding the structural mechanism by which proteins and peptides aggregate is crucial, given the role of fibrillar aggregates in debilitating amyloid diseases and bioinspired materials. Yet, this is a major challenge as the assembly involves multiple heterogeneous and transient intermediates. Here, we analyze the co-aggregation of Aβ40 and Aβ16–22, two widely studied peptide fragments of Aβ42 implicated in Alzheimer’s disease. We demonstrate that Aβ16–22 increases the aggregation rate of Aβ40 through a surface-catalyzed secondary nucleation mechanism. Discontinuous molecular dynamics simulations allowed aggregation to be tracked from the initial random coil monomer to the catalysis of nucleation on the fibril surface. Together, the results provide insight into how dynamic interactions between Aβ40 monomers/oligomers on the surface of preformed Aβ16–22 fibrils nucleate Aβ40 amyloid assembly. This new understanding may facilitate development of surfaces designed to enhance or suppress secondary nucleation and hence to control the rates and products of fibril assembly.

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Hornedo-Ortega, Ruth, María Antonia Álvarez-Fernández, Ana Belén Cerezo, Tristan Richard, Ana Marı́a Troncoso, and Marı́a Carmen Garcia-Parrilla. "Protocatechuic Acid: Inhibition of Fibril Formation, Destabilization of Preformed Fibrils of Amyloid-β and α-Synuclein, and Neuroprotection." Journal of Agricultural and Food Chemistry 64, no. 41 (October 10, 2016): 7722–32. http://dx.doi.org/10.1021/acs.jafc.6b03217.

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Kulkarni, Aishwarya S., Maria del Mar Cortijo, Elizabeth R. Roberts, Tamara L. Suggs, Heather B. Stover, José I. Pena-Bravo, Jennifer A. Steiner, Kelvin C. Luk, Patrik Brundin, and Daniel W. Wesson. "Perturbation of in vivo Neural Activity Following α-Synuclein Seeding in the Olfactory Bulb." Journal of Parkinson's Disease 10, no. 4 (October 27, 2020): 1411–27. http://dx.doi.org/10.3233/jpd-202241.

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Background: Parkinson’s disease (PD) neuropathology is characterized by intraneuronal protein aggregates composed of misfolded α-Synuclein (α-Syn), as well as degeneration of substantia nigra dopamine neurons. Deficits in olfactory perception and aggregation of α-Syn in the olfactory bulb (OB) are observed during early stages of PD, and have been associated with the PD prodrome, before onset of the classic motor deficits. α-Syn fibrils injected into the OB of mice cause progressive propagation of α-Syn pathology throughout the olfactory system and are coupled to olfactory perceptual deficits. Objective: We hypothesized that accumulation of pathogenic α-Syn in the OB impairs neural activity in the olfactory system. Methods: To address this, we monitored spontaneous and odor-evoked local field potential dynamics in awake wild type mice simultaneously in the OB and piriform cortex (PCX) one, two, and three months following injection of pathogenic preformed α-Syn fibrils in the OB. Results: We detected α-Syn pathology in both the OB and PCX. We also observed that α-Syn fibril injections influenced odor-evoked activity in the OB. In particular, α-Syn fibril-injected mice displayed aberrantly high odor-evoked power in the beta spectral range. A similar change in activity was not detected in the PCX, despite high levels of α-Syn pathology. Conclusion: Together, this work provides evidence that synucleinopathy impacts in vivo neural activity in the olfactory system at the network-level.

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Zhang, Wei, Ying Du, Miao Bai, Ye Xi, Zhuyi Li, and Jianting Miao. "Retracted: S14G-humanin inhibits Aβ1-42 fibril formation, disaggregates preformed fibrils, and protects against Aβ-induced cytotoxicity in vitro." Journal of Peptide Science 19, no. 3 (January 24, 2013): 159–65. http://dx.doi.org/10.1002/psc.2484.

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He, Jing, Yan-Fei Xing, Bo Huang, Yi-Zheng Zhang, and Cheng-Ming Zeng. "Tea Catechins Induce the Conversion of Preformed Lysozyme Amyloid Fibrils to Amorphous Aggregates." Journal of Agricultural and Food Chemistry 57, no. 23 (December 9, 2009): 11391–96. http://dx.doi.org/10.1021/jf902664f.

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Ardah, Mustafa T., Katerina E. Paleologou, Guohua Lv, Sindhu A. Menon, Salema B. Abul Khair, Jia-Hong Lu, Bared Safieh-Garabedian, et al. "Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils." Neurobiology of Disease 74 (February 2015): 89–101. http://dx.doi.org/10.1016/j.nbd.2014.11.007.

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Howe, Jacob W., Caryl E. Sortwell, Megan F. Duffy, Christopher J. Kemp, Christopher P. Russell, Michael Kubik, Pooja Patel, Kelvin C. Luk, Omar M. A. El-Agnaf, and Joseph R. Patterson. "Preformed fibrils generated from mouse alpha-synuclein produce more inclusion pathology in rats than fibrils generated from rat alpha-synuclein." Parkinsonism & Related Disorders 89 (August 2021): 41–47. http://dx.doi.org/10.1016/j.parkreldis.2021.06.010.

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Wang, Gang, Xinyi Zhu, Xiaona Song, Qingwen Zhang, and Zhenyu Qian. "Melatonin Inhibits hIAPP Oligomerization by Preventing β-Sheet and Hydrogen Bond Formation of the Amyloidogenic Region Revealed by Replica-Exchange Molecular Dynamics Simulation." International Journal of Molecular Sciences 23, no. 18 (September 6, 2022): 10264. http://dx.doi.org/10.3390/ijms231810264.

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The pathogenesis of type 2 diabetes (T2D) is highly related to the abnormal self-assembly of the human islet amyloid polypeptide (hIAPP) into amyloid aggregates. To inhibit hIAPP aggregation is considered a promising therapeutic strategy for T2D treatment. Melatonin (Mel) was reported to effectively impede the accumulation of hIAPP aggregates and dissolve preformed fibrils. However, the underlying mechanism at the atomic level remains elusive. Here, we performed replica-exchange molecular dynamics (REMD) simulations to investigate the inhibitory effect of Mel on hIAPP oligomerization by using hIAPP20–29 octamer as templates. The conformational ensemble shows that Mel molecules can significantly prevent the β-sheet and backbone hydrogen bond formation of hIAPP20–29 octamer and remodel hIAPP oligomers and transform them into less compact conformations with more disordered contents. The interaction analysis shows that the binding behavior of Mel is dominated by hydrogen bonding with a peptide backbone and strengthened by aromatic stacking and CH–π interactions with peptide sidechains. The strong hIAPP–Mel interaction disrupts the hIAPP20–29 association, which is supposed to inhibit amyloid aggregation and cytotoxicity. We also performed conventional MD simulations to investigate the influence and binding affinity of Mel on the preformed hIAPP1–37 fibrillar octamer. Mel was found to preferentially bind to the amyloidogenic region hIAPP20–29, whereas it has a slight influence on the structural stability of the preformed fibrils. Our findings illustrate a possible pathway by which Mel alleviates diabetes symptoms from the perspective of Mel inhibiting amyloid deposits. This work reveals the inhibitory mechanism of Mel against hIAPP20–29 oligomerization, which provides useful clues for the development of efficient anti-amyloid agents.

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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.

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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.

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Eze, Fredrick Nwude, Kornkanok Ingkaninan, and Porntip Prapunpoj. "Transthyretin Anti-Amyloidogenic and Fibril Disrupting Activities of Bacopa monnieri (L.) Wettst (Brahmi) Extract." Biomolecules 9, no. 12 (December 9, 2019): 845. http://dx.doi.org/10.3390/biom9120845.

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The homotetrameric plasma protein transthyretin (TTR), is responsible for a series of debilitating and often fatal disorders in humans known as transthyretin amyloidosis. Currently, there is no cure for TTR amyloidosis and treatment options are rare. Thus, the identification and development of effective and safe therapeutic agents remain a research imperative. The objective of this study was to determine the effectiveness of Bacopa monnieri extract (BME) in the modulation of TTR amyloidogenesis and disruption of preformed fibrils. Using aggregation assays and transmission electron microscopy, it was found that BME abrogated the formation of human TTR aggregates and mature fibrils but did not dis-aggregate pre-formed fibrils. Through acid-mediated and urea-mediated denaturation assays, it was revealed that BME mitigated the dissociation of folded human TTR and L55P TTR into monomers. ANS binding and glutaraldehyde cross-linking assays showed that BME binds at the thyroxine-binding site and possibly enhanced the quaternary structural stability of native TTR. Together, our results suggest that BME bioactives prevented the formation of TTR fibrils by attenuating the disassembly of tetramers into monomers. These findings open up the possibility of further exploration of BME as a potential resource of valuable anti-TTR amyloidosis therapeutic ingredients.

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Hu, Sheng-Quan, Rui Wang, Wei Cui, Shing-Hung Mak, Gang Li, Yuan-Jia Hu, Ming-Yuen Lee, Yuan-Ping Pang, and Yi-Fan Han. "Dimeric bis (heptyl)-Cognitin Blocks Alzheimer's β-Amyloid Neurotoxicity Via the Inhibition of Aβ Fibrils Formation and Disaggregation of Preformed Fibrils." CNS Neuroscience & Therapeutics 21, no. 12 (October 28, 2015): 953–61. http://dx.doi.org/10.1111/cns.12472.

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Corti, Roberta, Alysia Cox, Valeria Cassina, Luca Nardo, Domenico Salerno, Claudia Adriana Marrano, Natalia Missana, et al. "The Clustering of mApoE Anti-Amyloidogenic Peptide on Nanoparticle Surface Does Not Alter Its Performance in Controlling Beta-Amyloid Aggregation." International Journal of Molecular Sciences 21, no. 3 (February 5, 2020): 1066. http://dx.doi.org/10.3390/ijms21031066.

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The deposition of amyloid-β (Aβ) plaques in the brain is a significant pathological signature of Alzheimer’s disease, correlating with synaptic dysfunction and neurodegeneration. Several compounds, peptides, or drugs have been designed to redirect or stop Aβ aggregation. Among them, the trideca-peptide CWG-LRKLRKRLLR (mApoE), which is derived from the receptor binding sequence of apolipoprotein E, is effectively able to inhibit Aβ aggregation and to promote fibril disaggregation. Taking advantage of Atomic Force Microscopy (AFM) imaging and fluorescence techniques, we investigate if the clustering of mApoE on gold nanoparticles (AuNP) surface may affect its performance in controlling Aβ aggregation/disaggregation processes. The results showed that the ability of free mApoE to destroy preformed Aβ fibrils or to hinder the Aβ aggregation process is preserved after its clustering on AuNP. This allows the possibility to design multifunctional drug delivery systems with clustering of anti-amyloidogenic molecules on any NP surface without affecting their performance in controlling Aβ aggregation processes.

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Sulatskaya, Anna I., Georgy N. Rychkov, Maksim I. Sulatsky, Ekaterina V. Mikhailova, Nadezhda M. Melnikova, Veronika S. Andozhskaya, Irina M. Kuznetsova, and Konstantin K. Turoverov. "New Evidence on a Distinction between Aβ40 and Aβ42 Amyloids: Thioflavin T Binding Modes, Clustering Tendency, Degradation Resistance, and Cross-Seeding." International Journal of Molecular Sciences 23, no. 10 (May 15, 2022): 5513. http://dx.doi.org/10.3390/ijms23105513.

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The relative abundance of two main Abeta-peptide types with different lengths, Aβ40 and Aβ42, determines the severity of the Alzheimer’s disease progression. However, the factors responsible for different behavior patterns of these peptides in the amyloidogenesis process remain unknown. In this comprehensive study, new evidence on Aβ40 and Aβ42 amyloid polymorphism was obtained using a wide range of experimental approaches, including custom-designed approaches. We have for the first time determined the number of modes of thioflavin T (ThT) binding to Aβ40 and Aβ42 fibrils and their binding parameters using a specially developed approach based on the use of equilibrium microdialysis, which makes it possible to distinguish between the concentration of the injected dye and the concentration of dye bound to fibrils. The binding sites of one of these modes located at the junction of adjacent fibrillar filaments were predicted by molecular modeling techniques. We assumed that the sites of the additional mode of ThT-Aβ42 amyloid binding observed experimentally (which are not found in the case of Aβ40 fibrils) are localized in amyloid clots, and the number of these sites could be used for estimation of the level of fiber clustering. We have shown the high tendency of Aβ42 fibers to form large clots compared to Aβ40 fibrils. It is probable that this largely determines the high resistance of Aβ42 amyloids to destabilizing effects (denaturants, ionic detergents, ultrasonication) and their explicit cytotoxic effect, which we have shown. Remarkably, cross-seeding of Aβ40 fibrillogenesis using the preformed Aβ42 fibrils changes the morphology and increases the stability and cytotoxicity of Aβ40 fibrils. The differences in the tendency to cluster and resistance to external factors of Aβ40 and Aβ42 fibrils revealed here may be related to the distinct role they play in the deposition of amyloids and, therefore, differences in pathogenicity in Alzheimer’s disease.

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House, Emily, Matthew Mold, Joanna Collingwood, Alex Baldwin, Steven Goodwin, and Christopher Exley. "Copper Abolishes the β-Sheet Secondary Structure of Preformed Amyloid Fibrils of Amyloid-β42." Journal of Alzheimer's Disease 18, no. 4 (November 12, 2009): 811–17. http://dx.doi.org/10.3233/jad-2009-1235.

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45

Roux, Amandine, Xinhe Wang, Katelyn Becker, and Jiyan Ma. "Modeling α-Synucleinopathy in Organotypic Brain Slice Culture with Preformed α-Synuclein Amyloid Fibrils." Journal of Parkinson's Disease 10, no. 4 (October 27, 2020): 1397–410. http://dx.doi.org/10.3233/jpd-202026.

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Background: Synucleinopathy is a group of neurodegenerative disorders characterized by neurodegeneration and accumulation of alpha-synuclein (α-syn) aggregates in various brain regions. The detailed mechanism of α-syn-caused neurotoxicity remains obscure, which is partly due to the lack of a suitable model that retains the in vivo three-dimensional cellular network and allows a convenient dissection of the neurotoxic pathways. Recent studies revealed that the pre-formed recombinant α-syn amyloid fibrils (PFFs) induce a robust accumulation of pathogenic α-syn species in cultured cells and animals. Objective: Our goal is to determine whether PFFs are able to induce the pathogenic α-syn accumulation and neurotoxicity in organotypic brain slice culture, an ex vivo system that retains the in vivo three-dimensional cell-cell connections. Methods/Results: Adding PFFs to cultured wild-type rat or mouse brain slices induced a time-dependent accumulation of pathogenic α-syn species, which was indicated by α-syn phosphorylated at serine 129 (pα-syn). The PFF-induced pα-syn was abolished in brain slices prepared from α-syn null mice, suggesting that the pα-syn is from the phosphorylation of endogenous α-syn. Human PFFs also induced pα-syn in brain slices prepared from mice expressing human α-syn on a mouse α-syn-null background. Furthermore, the synaptophysin immunoreactivity was inversely associated with pα-syn accumulation and an increase of neuronal loss was detected. Conclusion: PFF-treatment of brain slices is able to induce key pathological features of synucleinopathy: pα-syn accumulation and neurotoxicity. This model will be useful for investigating the neurotoxic mechanism and evaluating efficacy of therapeutic approaches.

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46

Hu, Po-Sheng, Natalia Tomasovicova, Hsiu-Jen Chou, Meng-Chang Li, Marek Vojtko, Katarina Zakutanska, Jozefina Majorosova, Shean-Jen Chen, and Peter Kopcansky. "Hyperthermia Induced by Near-Infrared Laser-Irradiated CsWO3 Nanoparticles Disintegrates Preformed Lysozyme Amyloid Fibrils." Nanomaterials 10, no. 3 (February 29, 2020): 442. http://dx.doi.org/10.3390/nano10030442.

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This research study attempts to prove the concept of the applicability of hyperthermia to treating the lysozyme amyloid fibrils (LAFs)’s self-assembled fibrillary aggregates by a feedback-modulated temperature controller ranging from 26 °C to 80 °C, and separately, by near-infrared (NIR) laser-irradiated cesium tungstate (CsWO3) nanoparticle (NPs). The dependence of the final morphology of the amyloidal assembly on external heating and the photothermal effect of the NPs on treating the fibrillary assembly were investigated and analyzed. Experimentally, atomic force microscopy (AFM), optical stereoscopy, and scanning electron microscopy (SEM) were used primarily to ensure mutual interaction between LAFs and NPs, optically elucidate the surface contour and final fibrillary assembly upon the influence of thermal treatment, and further reveal fine-details of the optical samples. Finally, conclusive remarks are drawn that the fibrillary structures doped with the NPs exhibit an increasing degree of unique orthogonality. As the temperature rises, utter deformation of the dendritic structures of fibrillary assemblies at 70 °C was found, and NIR laser-irradiated CsWO3 NPs have been demonstrated to be useful in topically destructing pre-assembled LAFs, which may be conducive to the future development of neurodegenerative therapeutic techniques.

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Ray, Indrani, Abha Chauhan, Jerzy Wegiel, and Ved P. S. Chauhan. "Gelsolin inhibits the fibrillization of amyloid beta-protein, and also defibrillizes its preformed fibrils." Brain Research 853, no. 2 (January 2000): 344–51. http://dx.doi.org/10.1016/s0006-8993(99)02315-x.

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LU, YAN, WENHUI XI, and GUANGHONG WEI. "STRUCTURAL INSIGHT INTO THE POLYMORPHISM OF NNQNTF PROTOFIBRIL: IMPORTANCE OF INTERFACIAL WATER, POLAR AND AROMATIC RESIDUES." Journal of Theoretical and Computational Chemistry 12, no. 08 (December 2013): 1341012. http://dx.doi.org/10.1142/s0219633613410125.

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Polymorphism is widely observed in amyloid fibrils associated with many neurodegenerative diseases. Recent experimental study reported that fibrils formed by the segment NNQNTF of elk prion protein exhibited facial polymorphism with the two β-sheets either in back-to-back (BB) or in face-to-face (FF) packing arrangement. In the BB packing, the side chains of N2, N4 and F6 are interdigitated to form steric zipper, while in the FF packing, the side chains of N1, Q3 and T5 form the interdigitated interface. In this study, we investigate the water-mediated assembly of two preformed β-sheets and the physical interactions that stabilize the two different fibrils using all-atom molecular dynamics (MD) simulations. Multiple MD simulations have been carried out by starting from FF or BB packing of two β-sheets according to the facial polymorphism revealed by X-ray microcrystallography. For both packing patterns, we observe that the assembly of β-sheets is mediated by water molecules in the interface between β-sheets, leading to a long-lived protofibrils with wet interface prior to the formation of dry amyloid fibrils. Detailed structural analysis shows that besides the side chain steric zipper interactions, intra-sheet hydrogen bonding and aromatic stacking interactions play an important role on the stabilization of the protofibril with BB packing, while the intra-sheet and inter-sheet hydrogen bonding interactions are crucial for the formation of BB protofibril. These findings provide insights into the mechanism that lead to the facial polymorphism of NNQNTF fibrils.

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Paul, Ashim, Guru KrishnaKumar Viswanathan, Adi Huber, Elad Arad, Hamutal Engel, Raz Jelinek, Ehud Gazit, and Daniel Segal. "Inhibition of tau amyloid formation and disruption of its preformed fibrils by Naphthoquinone–Dopamine hybrid." FEBS Journal 288, no. 14 (February 18, 2021): 4267–90. http://dx.doi.org/10.1111/febs.15741.

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Domanskyi, Andrii, and Piotr Chmielarz. "Alpha-synuclein preformed fibrils: a tool to understand Parkinson’s disease and develop disease modifying therapy." Neural Regeneration Research 16, no. 11 (2021): 2219. http://dx.doi.org/10.4103/1673-5374.310686.

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