Dissertations / Theses on the topic 'Α-synuclein aggregation'
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Oliveira, Márcia Santos. "Modulation of α-synuclein aggregation and toxicity." Master's thesis, Faculdade de Ciências e Tecnologia, 2013. http://hdl.handle.net/10362/11195.
Full textIt is widely known that α-synuclein (aSyn) is an amyloidogenic protein prone to aggregation. This protein is found in specific inclusions named Lewy bodies in the surviving neurons of Parkinsons’s disease patients and other synucleinopathy brains. This aggregation process is greatly affected by different post-translational modifications, such as phosphorylation, acetylation, and glycation. Lately it was shown that aSyn oligomeric species are more toxic than the inclusion bodies. Heat shock proteins (HSPs) are molecular chaperones able to modulate the folding and refolding of proteins. Its overexpression in Parkinson’s disease models reduces and prevents aSyn aggregation. As the reduction of aSyn aggregation can lead to an eventual accumulation of oligomeric species which may cause cell damage, the main goal of this work is to better understand the role of HSPs in aSyn oligomer formation, clarifying which are the aSyn resulting species formed in the presence of HSPs. Moreover, as glycation is suggested to accelerate abnormal protein deposition, we aimed to investigate how HSPs interfere with the oligomerization process of glycated aSyn. In this study Hsp70 seemed to induce recombinant aSyn oligomerization, generating higher molecular weight species with no associated toxicity. On the other hand, Hsp27 reduced aSyn oligomerization in vitro possibly by inducing the formation of non-reactive small oligomers. MGO glycation increased protein aggregation and cell death. Interestingly, Hsp27 overexpression reversed glycated aSyn aggregation and its associated toxicity. These results demonstrate the importance of HSPs modulation as a possible target of Parkinson’s disease therapeutics.
Waudby, Christopher Andrew. "Structural and biophysical studies of α-synuclein and protein aggregation." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611252.
Full textPiroska, Marian-Leonard. "Engineering artificial biomolecular condensates to study the aggregation of α-Synuclein." Electronic Thesis or Diss., Sorbonne université, 2023. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2023SORUS542.pdf.
Full textNeurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's disease, are incurable illnesses characterized by the progressive degeneration of neurons, leading to cognitive and motor deficits in affected individuals. The development of effective treatments is currently limited by our incomplete understanding of the underlying mechanisms that drive disease initiation and progression. One prevailing characteristic observed in the tissues affected by neurodegenerative diseases is the presence of aggregated proteins, which have become hallmarks of diseases such as Parkinson’s and Alzheimer’s. Thus, the aggregation process is believed to play a pivotal role in disease pathogenesis. However, the specific mechanisms underlying the transition of soluble proteins to their aggregated state remain elusive. Recent research has proposed phase separation (PS) as a critical intermediate step in the formation of protein aggregates. PS is a physical phenomenon wherein certain proteins undergo a phase transition, forming distinct liquid-like droplets within the cellular environment. Biomolecular condensates are involved in various physiological cellular processes, but are also increasingly believed to be subject to aberrant behaviours that can trigger pathological conditions. Although promising, studying the role of PS in the context of neurodegenerative diseases is a challenging task, due to the intricate composition of cellular condensates. They consist of tens to hundreds of different biomolecules, including proteins, nucleic acids, and lipids, creating a complex milieu that demands innovative research approaches. To improve the study of LLPS in the context of neurodegenerative diseases, we have developed a method for the controlled formation and dissolution of biomolecular condensates enriched in proteins involved in pathological aggregation. First, we created condensates containing α-synuclein (α-Syn), the main pathological factor in Parkinson’s disease and other pathologies. α-Syn is known as a prion-like protein, meaning that its aggregates spreads from cell to cell and template the aggregation of soluble cytosolic α-Syn, promoting the progression of the disease. However, little is known about this phenomenon with respect to the condensed state of the protein. To simulate this phenomenon, we exposed cells expressing our α-Syn condensates to preformed α-Syn aggregates in fibrillar form. We observed that fibrils triggered the transition of condensates from their liquid-like state to an aggregated form with solid-like properties and exhibiting biochemical markers characteristic of amyloids. This allowed us to propose a model where the condensed phase of α-Syn speeds up the propagation of pathological aggregates, by providing a pool of concentrated protein that can undergo more easily an amyloid transition via the prion-like pathway. Subsequently, we have built artificial condensates enriched in α-Syn together with synapsin. In neurons, α-Syn and synapsin interact at the presynaptic termini, where they play an important role in the release of neurotransmitters by controlling the clustering, trafficking and release of membrane-enclosed neurotransmitter containers called synaptic vesicles. In our setting α-Syn/synapsin condensates were also subject to a liquid-to-solid transition mediated by α-Syn fibrils
Rcom-H'cheo-Gauthier, Alexandre Nay. "The Protective Effect of Calbindin-D28K on a-Synuclein Aggregation in α- Synucleinopathies." Thesis, Griffith University, 2016. http://hdl.handle.net/10072/368168.
Full textThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Griffith Health
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Peduzzo, Alessia [Verfasser]. "Mechanistic insights into α-synuclein aggregation: from fibril stability to surface nucleation / Alessia Peduzzo." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2019. http://d-nb.info/1201881978/34.
Full textRivers, Robert Clay. "Biophysical analysis of the aggregation behaviour and structural properties of α- and β-synuclein." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612821.
Full textCheruvara, Harish. "Intracellular peptide library screening to derive inhibitors of Parkinson's disease associated α-synuclein aggregation." Thesis, University of Essex, 2015. http://repository.essex.ac.uk/16040/.
Full textFillon, Gwenaëlle. "Pathologies associated to α-synuclein aggregation in primary culture models of multiple system atrophy." Paris 6, 2006. http://www.theses.fr/2006PA066030.
Full textRoman, Andrei. "Tau protein aggregation and α-synuclein dysfunction : development of new in vitro and in vivo models to study neurodegenerative diseases." Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0281.
Full textThe histopathological hallmarks of the most common neurodegenerative diseases – Alzheimer’s disease and Parkinson’s disease are neurofibrillary tangles formed by tau protein and Lewy bodies inclusions formed by aggregated α-synuclein. The formation and accumulation of these proteins into inclusions cause functional disruptions of the cytoskeleton and leads to neuronal degeneration. The precise mechanisms of tau and synuclein misfolding and aggregation leading to those cellulare incluses, even though very studied, are not fully understood neither for tau protein nor for α-synuclein.Here we have addressed this question using both in vitro and in vivo models. Investigating tau aggregation in vitro, we have found a reversible self-assembly of tau, which depends on temperature and is induced by zinc ions, which is different from the tau aggregation in the presence of aggregation-inducers such as heparin. This process could be implicated in the first steps of tau pathological aggregation. In a second part, we have developed a mouse model for studying the α-synuclein dysfunction. We have shown that α- synuclein is directly involved in the embryonic development of the specific regions of the nervous system, and that it has modulating effect only on the populations of dopaminergic neurons of substantia nigra, which are affected in Parkinson’s disease.Results obtained in our studies of two proteins that undergo pathogenic aggregation and form intracellular inclusions contributed to understanding of molecular and cellular processes associated with neuronal degeneration, which is important for the development of new disease-modifying therapies of neurodegenerative disorders
APRILE, FRANCESCO ANTONIO. "Extrinsic factors affecting amyloid aggregation." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2012. http://hdl.handle.net/10281/27834.
Full textAbeyawardhane, Dinendra L. "Biometal-Induced Structural Consequences of α-Synuclein – the Parkinson’s Disease Protein." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5909.
Full textGoodwin, Jacob J. "The Role of Calcium in Alpha-Synuclein Aggregation: A Potential Mechanism of Neurodegeneration." Thesis, Griffith University, 2014. http://hdl.handle.net/10072/366325.
Full textThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Griffith Health
Full Text
Gauhar, Aziz Verfasser], Wolfgang [Akademischer Betreuer] Hoyer, and Dieter [Akademischer Betreuer] [Willbold. "Engineering and characterization of a binder to inhibit in vivo α-synuclein aggregation / Aziz Gauhar. Gutachter: Wolfgang Hoyer ; Dieter Willbold." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2015. http://d-nb.info/1069620130/34.
Full textGauhar, Aziz [Verfasser], Wolfgang Akademischer Betreuer] Hoyer, and Dieter [Akademischer Betreuer] [Willbold. "Engineering and characterization of a binder to inhibit in vivo α-synuclein aggregation / Aziz Gauhar. Gutachter: Wolfgang Hoyer ; Dieter Willbold." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2015. http://nbn-resolving.de/urn:nbn:de:hbz:061-20150413-132245-0.
Full textAntonschmidt, Leif [Verfasser]. "On the molecular basis of α-synuclein aggregation on phospholipid membranes in the presence and absence of anle138b / Leif Antonschmidt." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2020. http://d-nb.info/1222265052/34.
Full textORDAZZO, GABRIELE. "Deciphering the defects of vesicle trafficking in RAB39B forms of Parkinson’s disease with implication in autophagy, α-Synuclein aggregation and dopaminergic presynaptic system alteration." Doctoral thesis, Università Vita-Salute San Raffaele, 2021. http://hdl.handle.net/20.500.11768/121784.
Full textLe proteine Rab, che lavorano come controllori essenziali della dinamica della membrana cellulare, recentemente associate a diversi percorsi patologici della malattia di Parkinson (MdP). In particolare, le varianti patogene di RAB39B causano disabilità intellettiva e MdP ad esordio precoce legato all'X con patologia cerebrale α-Sinucleina (α-Syn). In particolare, il gene RAB39B è specifico per il cervello, altamente espresso nei neuroni coinvolti principalmente nel traffico di vescicole intracellulari delle vie secretorie dell'ER-Golgi-endosoma, ma è stato scoperto che lavora nella formazione e nel mantenimento delle sinapsi. L'obiettivo generale di questo lavoro è trovare nuove intuizioni sul suo ruolo sconosciuto nella patogenesi del MdP e quale meccanismo potrebbe portare alla debolezza neuronale nel deficit autofagico di aggregati cellulari tossici e nell'alterazione dopaminergica presinaptica (DA). Al fine di identificare gli effettori RAB39B e le funzioni molecolari chiave a valle, il suo interactoma è stato identificato grazie all'implementazione del sistema di etichettatura APEX2 direttamente sulla coltura neuronale vivente. Attraverso questo approccio biochimico, stabiliamo un nuovo legame tra RAB39B e i complessi retromeri, con conseguenze funzionali sullo smistamento del carico come per M6PR, ATG9 o ATG9. Studiando i suoi interattori, ci siamo concentrati sulla funzione di traffico vescicolare e di membrana durante la formazione dell'autofagosoma nascente. Abbiamo ipotizzato che la perdita di funzione di RAB39B potrebbe portare a un difetto nella degradazione autofagica degli aggregati α-Syn nei neuroni. Sulla base di ciò, abbiamo intossicato neuroni primari di topo e neuroni RAB39B-knock out (KO) di derivazione umana con fibrille preformate α-Syn (PFF) per sottolineare la risposta del sistema autofagico, trovando alterazioni significative nei marcatori canonici LC3 e P62. Inoltre, per valutare la diffusione di α-Syn, l'aggregazione e la tipica neurodegenerazione DA, iniettiamo PFFs direttamente nel cervello dei topi RAB39b-KO. Inoltre, a causa del suo arricchimento del ruolo sinaptico, ci siamo concentrati sull'alterazione del sistema presinaptico nei topi RAB39b-KO. L'assenza di RAB39B può alterare la formazione, la funzione e il riciclo delle vescicole presinaptiche con alterazioni morfologiche e di densità delle vescicole sinaptiche, portando a una profonda riduzione del rilascio di dopamina striatale. Abbiamo trovato neurodegenerazione DA concomitante e perdita del livello di proteina VMAT2 in modo dipendente dall'età nei topi RAB39b-KO. In conclusione, i nostri risultati dimostrano una forte interazione tra la perdita di funzione di RAB39B nello sviluppo precoce del MdP con l'accumulo di α-Syn e la neurodegenerazione di DA sia in vitro che in vivo. Il nostro lavoro si concentra su associazioni prospettiche di interattori biologici, combinando dati murini e umani, fornendo una valutazione completa del fenotipo della malattia.
Wördehoff, Michael Verfasser], Dieter [Gutachter] [Willbold, and Wolfgang [Gutachter] Hoyer. "The Kinetics of α-Synuclein Aggregation: Single Fibril Growth, β1-β2 Contacts, Membrane Environments and Dityrosine Formation / Michael Wördehoff ; Gutachter: Dieter Willbold, Wolfgang Hoyer." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2017. http://d-nb.info/1139891189/34.
Full textPounot, Kevin. "Dynamique des agrégats et fibres pathologiques Water restructuring upon α-synuclein fibril formation induces an increase of dynamics and entropy Tracking internal and global diffusive dynamics during protein aggregation by high-resolution neutron spectroscopy." Thesis, Université Grenoble Alpes, 2020. http://www.theses.fr/2020GRALY014.
Full textNeurodegenerative diseases, such as Parkinson's and Alzheimer's, constitute a growingthreat with ever increasing prevalence. These diseases are characterized by the presence ofprotein deposits in the patient's brain that are called amyloids. Several proteins wereidentified in these deposits as being the molecular hallmark of the disorder, among whichwe can cite alpha-synuclein for Parkinson’s disease and tau for Alzheimers’s disease.Protein amyloid aggregation is central to neurodegenerative diseases and hence constitutesa target of choice for diagnostic and therapeutic attempts. Itis characterized by the formation of a structural cross-beta pattern, which is a stack ofbeta-sheets, usually forming long fibrils. Under specific conditions, larger aggregates can beobtained, such as micrometer-sized particles, including so-called particulates andspherulites. Several pieces of evidence suggest that the formation of such aggregates, and especially at early-stages, can be involved in protein toxicity. Yet, the reasons for theaggregation to occur are not well understood. In this work, we aimed at deciphering thefundamental principles underlying protein amyloid aggregation by studying the changesin protein ad hydration water dynamics, the understanding of which might help in the development ofwater-dynamics based diagnostic methods.We employed mainly incoherent neutron scattering (on SPHERES at the MLZ and IN16B at the ILL)and molecular dynamics simulations. Theformer provides ensemble averaged information on hydrogen motions in the system, and thelatter provides a fully atomistic picture from which dynamical and structural aspects canbe investigated.Studying alpha-synuclein, we could show that protein backbone and side-chain motions - that is,internal dynamics - is barely affected by aggregation. However, hydration water motions areincreased around amyloid fibrils. The increased dynamics originates from a fraction ofwater molecules being displaced from the protein hydrophobic core to the hydrophilictermini regions when fibrils are formed. Hence, it results in a higher water entropy in fibrils,where the central cross-beta pattern appears highly efficient in protecting itself frominteracting with the solvent.For gammaS-crystallin, comparison of the internal protein dynamics of the wild-type proteinwith a G18V mutant revealed that the mutant is less dynamic, whatever itsaggregation state. This observation, along with the comparison of protein dynamics withtheir relative hydropathy index, indicates that the internal dynamics depends strongly onthe amino acid composition, but not on the aggregation state. In addition, other factorscan affect protein dynamics, such as the presence of metal ions.The measurements carriedout on insulin, in the presence or absence of zinc show that the metal promotes proteinhydration at pH 1.8, where it interacts loosely with the protein. The zincaffects also aggregate-aggregate interaction, probably by electrostatic screening as theformation of spherulites is facilitated in the absence of the metal.Eventually, the possibility to unambiguously and simultaneously access internal dynamicsand center-of-mass diffusion was demonstrated by carrying out so-called fixed- window scanson the IN16B instrument at the ILL. This novel technique applied to lysozyme showed thatparticulate formation occurs in a one-step process, and the internal dynamics remainsconstant all along. This pilot experiment opens up the possibility to study fibrilformation of pathologically relevant proteins.Taken together, the aforementioned results demonstrate that we can now study the amyloidaggregation process with great detail, and there is a great opportunity to extend this workwithin a biological context, in order to link the biophysical properties of protein amyloidaggregation with its effects and toxicity in-vivo
Bourdenx, Mathieu. "Approche multifactorielle de la dégénérescence parkinsonienne." Thesis, Bordeaux, 2015. http://www.theses.fr/2015BORD0135/document.
Full textThe aim of this work was to focus on neurodegenerative mechanisms in the context of synucleinopathies, especially on Parkinson’s disease (PD). PD is characterized by the loss of dopaminergic neurons and the presence of intracytoplasmic proteinaceous inclusions named Lewy Bodies of which α-synuclein (α-syn) is the main protein component. To date, there are no curative treatments. Elucidating mechanisms underlying neurodegeneration in PD will allow the identification of new molecular targets for therapeutic intervention. My Ph.D. work intends multifactorial and translational approaches based on modelling, therapeutic intervention and mechanistic studies. We first focused on the development of new animal models of PD based on the use of viral vector-mediated overexpression of α-syn. This word allowed us to conclude on the absence of additive effect of ageing in α-syn-related toxicity, at least in the three investigated species. Then, we worked on two therapeutic strategies to overcome the lysosomal dysfunction occurring in PD. To do so, we first developed a biotechnological approach based on the use of acidic nanoparticles restoring acidic pH of sick lysosomes, and then we used a gene therapy approach based on the overexpression on a central modulator lysosomal biogenesis. We here demonstrated the interest of restoration of lysosomal physiology. Finally, we tested the “prion-like” hypothesis in a cohort of nonhuman primates and assessed the efficacy of a therapeutic approach using an oligomer modulator in mice. This work highlights the central role of α-syn in PD etiology and offers innovative strategies for both modelling and therapeutic intervention
Schmidt, Felix. "Toxische Oligomere in der Pathogenese des Morbus Parkinson - Elektrophysiologische Charakterisierung der Membraninteraktion und Porenbildung von pathologischen α-Synuclein Aggregaten." Diss., Ludwig-Maximilians-Universität München, 2014. http://nbn-resolving.de/urn:nbn:de:bvb:19-168868.
Full textSchmidt, Felix Verfasser], and Armin [Akademischer Betreuer] [Giese. "Toxische Oligomere in der Pathogenese des Morbus Parkinson - Elektrophysiologische Charakterisierung der Membraninteraktion und Porenbildung von pathologischen α-Synuclein Aggregaten / Felix Schmidt. Betreuer: Armin Giese." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2014. http://d-nb.info/1051258634/34.
Full textChan, Tiffiny. "Electroanalysis of α-Synuclein Aggregation Related to Parkinson's Disease." Thesis, 2011. http://hdl.handle.net/1807/29507.
Full textKrumova, Petranka. "SUMOylation modulates α-synuclein toxicity and fibril formation." Doctoral thesis, 2009. http://hdl.handle.net/11858/00-1735-0000-0006-B50A-6.
Full textLázaro, Diana Fernandes. "Systematic comparison of the effects of α-synuclein mutations on aggregation in Parkinson’s Diseases." Master's thesis, 2012. http://hdl.handle.net/10451/7246.
Full textO envelhecimento da população humana está associado ao aumento da incidência de doenças neurodegenerativas, como a doença de Parkinson (DP) e a doença de Alzheimer. O misfolding e subsequente agregação de proteínas é uma característica patológica presente em diferentes doenças neurodegenerativas. No entanto, permanece por esclarecer se tais eventos se tratam de uma causa ou uma consequência da progressão da doença. O primeiro gene implicado na DP foi SNCA que codifica a proteína alfa-sinucleína (aSyn), principal proteína que compõe os corpos de Lewy (LB), agregados proteicos que se acumulam nos neurónios dos pacientes com DP. É igualmente conhecido que a sobre expressão da aSyn em vários modelos animais com DP resulta em citotoxicidade. A maioria dos casos DP são esporádicos, no entanto cerca de ~5-10% de casos familiares estão ligados a mutações específicas em diferentes genes. Até ao momento, são conhecidas três mutações no gene que codifica aSyn e que se encontram igualmente associado à etiologia dos casos familiares de DP. No entanto, os mecanismos pelos quais cada mutação leva à doença, são ainda desconhecidos. O objetivo deste projeto é investigar o efeito das diferentes mutações na formação de inclusões de aSyn ligada aos casos familiares (A30P, E4K e A53T), bem como mutações artificiais, conhecidas por interferirem com a biologia da agregação de aSyn (S129A, S129D, S87A, S87E, tripla prolina, Y125). Espera-se que esta análise comparativa forneça informações importantes sobre os mecanismos moleculares envolvidos no processo agregação/misfolding da aSyn, permitindo assim o desenvolvimento de novas e estratégias de intervenção na DP e outras sinucleinopatias.
The aging of the human population is associated with an increased incidence of neurodegenerative diseases, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). Protein misfolding and aggregation is one of the pathological hallmarks present in different neurodegenerative disorders, but it is still unclear whether this is a cause or a consequence of the disease progression. The first gene implicated in PD was SNCA. This gene encodes alpha-synuclein protein (aSyn), which is the main protein component of Lewy bodies (LB). LBs are protein inclusions that accumulate in living neurons of PD patients. It is known that, when overexpressed, aSyn results in an increase of cytotoxicity, in several cell-based and animal models of PD. The majority of PD cases are sporadic and only ~5-10% are linked to familial cases and are associated with a specific gene mutation. To date, three mutations in the gene encoding aSyn are known, suggesting that it also plays a major role in the etiology of familial cases of PD. Nevertheless, the mechanisms through which each mutation leads to disease, are still not known. The purpose of this study is to investigate the effect of inclusion formation of different familial aSyn mutations (A30P, E4K and A53T), as well as artificial mutations that are known to interfere with the normal biology and aggregation of the protein (S129A, S129D, S87A, S87E, Triple proline mutation, Y125). Ultimately, this comparative analysis will provide important insight into the molecular mechanisms involved in the misfolding/aggregation process and may enable the development of novel strategies, for intervention in PD and other synucleinopathies.
Mehnert, Thomas [Verfasser]. "Untersuchungen zur Faltung und spontanen Aggregation des amyloidogenen Proteins α-Synuclein [Alpha-Synuclein] sowie zur Interaktion mit Sphingomyelin-Domänen / Thomas Mehnert." 2004. http://d-nb.info/972308970/34.
Full textBertoncini, Carlos Walter [Verfasser]. "Structure and dynamics of the aggregation mechanism of the Parkinson's disease-associated protein α-synuclein [alpha-synuclein] / vorgelegt von Carlos Walter Bertoncini." 2006. http://d-nb.info/981835260/34.
Full textAntonschmidt, Leif. "On the molecular basis of α-synuclein aggregation on phospholipid membranes in the presence and absence of anle138b." Doctoral thesis, 2019. http://hdl.handle.net/21.11130/00-1735-0000-0005-1428-8.
Full textLu, Yea-Ting, and 呂雅婷. "Establishment of Neurotoxin-Induced and α-Synuclein Aggregation Parkinson’s Disease Cell Models as Drug Testing Platform." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/ntg8q2.
Full text國立臺灣師範大學
生命科學研究所
102
Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting people in their middle and old age. It is characterized by resting tremor, rigidity, akinesia and postural instability and associated with selected loss of dopaminergic (DA) neuron in the substantianigra pars compacta. Combinations of environmental and genetic factors are thought to cause PD. Among the genetic factors contributing to the pathogenesis of PD, mutations in the α-synuclein gene such as A30P, A53T and E46K increased aggregate formation and mutations in Parkin, DJ-1 and PINK1 impaired mitochondrial function. In addition, environmental factors as well as aging are also thought to contribute the development of the disease. No effective treatment for the disease currently urges the development of new agents that may halt the degeneration of PD. In this study, human neuroblastoma SH-SY5Y cells were differentiated toward the DA phenotype in the presence of retinoic acid (RA) follow by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Greatly up-regulated tyrosine hydroxylase (TH, DA neuronal marker) in SH-SY5Y cells was observed following 7 days of differentiation. These TH-positive cells exhibited a mature morphology with long, branched cell processes and large cell bodies. Addition of MPP+ (1-methyl-4-phenylpyridinium), a potent complex I inhibitor in DA neurons, to the above SH-SY5Y cells caused significant cell death compared with untreated cells. This MPP+-induced cell death was used to screen herbal extracts provided by Industrial Technology Research Institute (ITRI). Cell viability assay indicated that pretreatment of herbal extracts NTNU-043, -057, -059, -125, -293, -313, -331, -385, -450, and -514 protected undifferentiated SH-SY5Y cells against MPP+-induced toxicity, whereas pretreatment of herbal extracts NTNU-092 and -313 protected differentiated SH-SY5Y cells against MPP+-induced toxicity.
Bigi, Alessandra. "Study of the relationship between structure and toxicity of different α-synuclein aggregates and related cellular dysfunctions." Doctoral thesis, 2020. http://hdl.handle.net/2158/1191838.
Full textWender, Nora. "Cellular function and toxicity of the Parkinson’s disease-related genes α-synuclein and catp-6 in C. elegans." Doctoral thesis, 2012. http://hdl.handle.net/11858/00-1735-0000-0015-97E4-A.
Full textSlabá, Renata. "Charakteristika stresových granulí u kvasinky Saccharomyces cerevisiae." Master's thesis, 2011. http://www.nusl.cz/ntk/nusl-312712.
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