Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, 92-215 Lodz, Poland.
Int J Mol Sci. 2023 Dec 26;25(1):360. doi: 10.3390/ijms25010360.
Parkinson's disease (PD) is a complex neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra and the widespread accumulation of alpha-synuclein (αSyn) protein aggregates. αSyn aggregation disrupts critical cellular processes, including synaptic function, mitochondrial integrity, and proteostasis, which culminate in neuronal cell death. Importantly, αSyn pathology extends beyond neurons-it also encompasses spreading throughout the neuronal environment and internalization by microglia and astrocytes. Once internalized, glia can act as neuroprotective scavengers, which limit the spread of αSyn. However, they can also become reactive, thereby contributing to neuroinflammation and the progression of PD. Recent advances in αSyn research have enabled the molecular diagnosis of PD and accelerated the development of targeted therapies. Nevertheless, despite more than two decades of research, the cellular function, aggregation mechanisms, and induction of cellular damage by αSyn remain incompletely understood. Unraveling the interplay between αSyn, neurons, and glia may provide insights into disease initiation and progression, which may bring us closer to exploring new effective therapeutic strategies. Herein, we provide an overview of recent studies emphasizing the multifaceted nature of αSyn and its impact on both neuron and glial cell damage.
帕金森病（PD）是一种复杂的神经退行性疾病，其特征是黑质中多巴胺能神经元的进行性丧失和广泛积累的α-突触核蛋白（αSyn）蛋白聚集体。αSyn 聚集破坏了关键的细胞过程，包括突触功能、线粒体完整性和蛋白质稳态，最终导致神经元细胞死亡。重要的是，αSyn 病理学不仅局限于神经元 - 它还包括在神经元环境中的扩散以及被小胶质细胞和星形胶质细胞内化。一旦内化，胶质细胞可以作为神经保护的清道夫，限制αSyn 的扩散。然而，它们也可以变得反应性，从而导致神经炎症和 PD 的进展。αSyn 研究的最新进展使 PD 的分子诊断成为可能，并加速了靶向治疗的发展。然而，尽管经过了二十多年的研究，αSyn 的细胞功能、聚集机制以及对细胞损伤的诱导仍然不完全清楚。揭示αSyn、神经元和胶质细胞之间的相互作用可能为疾病的发生和进展提供深入的了解，从而使我们更接近探索新的有效治疗策略。本文提供了对最近研究的概述，强调了αSyn 的多面性及其对神经元和神经胶质细胞损伤的影响。
