Hyejin Park, Tae-In Kam, Valina L. Dawson, Ted M. Dawson
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引用次数: 0
摘要
α-突触核蛋白错误折叠成病理形式,导致各种神经退行性疾病,统称为α-突触核蛋白病。在本综述中,我们将全面概述α-突触核蛋白研究的重要进展。我们研究了α-突触核蛋白的结构特征和生理功能,并总结了目前对关键翻译后修饰(如硝化、磷酸化、泛素化、苏木酰化和截短)的见解,考虑了它们对神经退行性变的贡献。我们还强调了疾病特异性α-突触核蛋白菌株的存在及其病理扩散机制,并讨论了种子扩增测定和 PET 示踪剂作为在临床环境中检测病理α-突触核蛋白的新兴诊断工具。我们还讨论了α-突触核蛋白的聚集和清除机制,回顾了导致神经元死亡的细胞自主和非细胞自主过程,包括适应性免疫和先天性免疫在α-突触核蛋白驱动的神经变性中的作用。最后,我们重点介绍了针对病理性α-突触核蛋白的有前景的治疗方法,并对新兴研究领域提出了见解。
α-Synuclein pathology as a target in neurodegenerative diseases
α-Synuclein misfolds into pathological forms that lead to various neurodegenerative diseases known collectively as α-synucleinopathies. In this Review, we provide a comprehensive overview of pivotal advances in α-synuclein research. We examine structural features and physiological functions of α-synuclein and summarize current insights into key post-translational modifications, such as nitration, phosphorylation, ubiquitination, sumoylation and truncation, considering their contributions to neurodegeneration. We also highlight the existence of disease-specific α-synuclein strains and their mechanisms of pathological spread, and discuss seed amplification assays and PET tracers as emerging diagnostic tools for detecting pathological α-synuclein in clinical settings. We also discuss α-synuclein aggregation and clearance mechanisms, and review cell-autonomous and non-cell-autonomous processes that contribute to neuronal death, including the roles of adaptive and innate immunity in α-synuclein-driven neurodegeneration. Finally, we highlight promising therapeutic approaches that target pathological α-synuclein and provide insights into emerging areas of research.
期刊介绍:
Nature Reviews Neurology aims to be the premier source of reviews and commentaries for the scientific and clinical communities we serve. We want to provide an unparalleled service to authors, referees, and readers, and we work hard to maximize the usefulness and impact of each article. The journal publishes Research Highlights, Comments, News & Views, Reviews, Consensus Statements, and Perspectives relevant to researchers and clinicians working in the field of neurology. Our broad scope ensures that the work we publish reaches the widest possible audience. Our articles are authoritative, accessible, and enhanced with clearly understandable figures, tables, and other display items. This page gives more detail about the aims and scope of the journal.