Coskuner-Weber Orkid, Mirzanli Ozan, Uversky Vladimir N
Molecular Biotechnology, Turkish-German University, Sahinkaya Caddesi, No. 106, Beykoz, 34820 Istanbul, Turkey.
USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL USA.
Biophys Rev. 2022 Jun 8;14(3):679-707. doi: 10.1007/s12551-022-00968-0. eCollection 2022 Jun.
Many different intrinsically disordered proteins and proteins with intrinsically disordered regions are associated with neurodegenerative diseases. These types of proteins including amyloid-β, tau, α-synuclein, CHCHD2, CHCHD10, and G-protein coupled receptors are increasingly becoming evaluated as potential drug targets in the pharmaceutical-based treatment approaches. Here, we focus on the neurobiology of this class of proteins, which lie at the center of numerous neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, Huntington's disease, amyotrophic lateral sclerosis, frontotemporal dementia, Charcot-Marie-Tooth diseases, spinal muscular atrophy, and mitochondrial myopathy. Furthermore, we discuss the current treatment design strategies involving intrinsically disordered proteins and proteins with intrinsically disordered regions in neurodegenerative diseases. In addition, we emphasize that although the G-protein coupled receptors are traditionally investigated using structural biology-based models and approaches, current studies show that these receptors are proteins with intrinsically disordered regions and therefore they require new ways for their analysis.
许多不同的内在无序蛋白和含有内在无序区域的蛋白与神经退行性疾病相关。这类蛋白包括β-淀粉样蛋白、tau蛋白、α-突触核蛋白、CHCHD2、CHCHD10和G蛋白偶联受体，在基于药物的治疗方法中，它们越来越多地被评估为潜在的药物靶点。在此，我们聚焦于这类蛋白的神经生物学，它们处于众多神经退行性疾病的核心位置，如阿尔茨海默病、帕金森病、亨廷顿舞蹈症、肌萎缩侧索硬化症、额颞叶痴呆、夏科-马里-图斯病、脊髓性肌萎缩症和线粒体肌病。此外，我们讨论了目前针对神经退行性疾病中内在无序蛋白和含有内在无序区域的蛋白的治疗设计策略。另外，我们强调，尽管传统上使用基于结构生物学的模型和方法来研究G蛋白偶联受体，但目前的研究表明这些受体是含有内在无序区域的蛋白，因此它们需要新的分析方法。
