کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8648250 | 1570441 | 2018 | 46 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Polyglutamine expansion diseases: More than simple repeats
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کلمات کلیدی
MJDhttNLSAtaxin-3DRPLANTDSBMAPolyQCBPCDK2CACNA1ATRICDeubiquitinaseDUBSUMOTBPGSK 3βPTMVCP/p97AlphaB-crystallinAtx1nuclear magnetic resonance - رزونانس مغناطیسی هستهایdentatorubral-pallidoluysian atrophy - آتروفی dentatorubral-pallidoluysianApr - آوریلAkt - آکتataxin-1 - اتاکسین-1post-translational modification - اصلاح post-translationalMachado-Joseph disease - بیماری ماچادو جوزفHuntington’s disease - بیماری هانتینگتونNeurodegenerative disease - بیماری های نوروژنیکNMR - تشدید مغناطیسی هستهای N-terminal domain - دامنه N-terminalnuclear localization sequence - دنباله محلی سازی هسته ایHuntingtin - هانتینگتنCREB-binding protein - پروتئین اتصال CREBTATA-binding protein - پروتئین متصل به TATAprotein kinase B - پروتئین کیناز BPolyglutamine - پلیگلوتامینCHiP - چیپsmall ubiquitin-like modifier - کوچک مانند ubiquitin مانند اصلاح کنندهCoiled-coil - کویل کویلGlycogen synthase kinase 3β - گلیکوزین سنتاز کیناز 3βAndrogen Receptor - گیرنده آندروژنی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Polyglutamine (polyQ) repeat-containing proteins are widespread in the human proteome but only nine of them are associated with highly incapacitating neurodegenerative disorders. The genetic expansion of the polyQ tract in disease-related proteins triggers a series of events resulting in neurodegeneration. The polyQ tract plays the leading role in the aggregation mechanism, but other elements modulate the aggregation propensity in the context of the full-length proteins, as implied by variations in the length of the polyQ tract required to trigger the onset of a given polyQ disease. Intrinsic features such as the presence of aggregation-prone regions (APRs) outside the polyQ segments and polyQ-flanking sequences, which synergistically participate in the aggregation process, are emerging for several disease-related proteins. The inherent polymorphic structure of polyQ stretches places the polyQ proteins in a central position in protein-protein interaction networks, where interacting partners may additionally shield APRs or reshape the aggregation course. Expansion of the polyQ tract perturbs the cellular homeostasis and contributes to neuronal failure by modulating protein-protein interactions and enhancing toxic oligomerization. Post-translational modifications further regulate self-assembly either by directly altering the intrinsic aggregation propensity of polyQ proteins, by modulating their interaction with different macromolecules or by modifying their withdrawal by the cell quality control machinery. Here we review the recent data on the multifaceted aggregation pathways of disease-related polyQ proteins, focusing on ataxin-3, the protein mutated in Machado-Joseph disease. Further mechanistic understanding of this network of events is crucial for the development of effective therapies for polyQ diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Structural Biology - Volume 201, Issue 2, February 2018, Pages 139-154
Journal: Journal of Structural Biology - Volume 201, Issue 2, February 2018, Pages 139-154
نویسندگان
Alexandra Silva, Ana Viana de Almeida, Sandra Macedo-Ribeiro,