Department of Neurodegeneration Diagnostics, Medical University of Białystok, 15-089 Białystok, Poland.
Department of Biochemical Diagnostics, University Hospital in Białystok, 15-269 Białystok, Poland.
Int J Mol Sci. 2024 Aug 24;25(17):9197. doi: 10.3390/ijms25179197.
A presynaptic protein called α-synuclein plays a crucial role in synaptic function and neurotransmitter release. However, its misfolding and aggregation have been implicated in a variety of neurodegenerative diseases, particularly Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Emerging evidence suggests that α-synuclein interacts with various cellular pathways, including mitochondrial dysfunction, oxidative stress, and neuroinflammation, which contributes to neuronal cell death. Moreover, α-synuclein has been involved in the propagation of neurodegenerative processes through prion-like mechanisms, where misfolded proteins induce similar conformational changes in neighboring neurons. Understanding the multifaced roles of α-synuclein in neurodegeneration not only aids in acquiring more knowledge about the pathophysiology of these diseases but also highlights potential biomarkers and therapeutic targets for intervention in alpha-synucleinopathies. In this review, we provide a summary of the mechanisms by which α-synuclein contributes to neurodegenerative processes, focusing on its misfolding, oligomerization, and the formation of insoluble fibrils that form characteristic Lewy bodies. Furthermore, we compare the potential value of α-synuclein species in diagnosing and differentiating selected neurodegenerative diseases.
一种名为α-突触核蛋白的突触前蛋白在突触功能和神经递质释放中起着关键作用。然而，其错误折叠和聚集与多种神经退行性疾病有关，特别是帕金森病、路易体痴呆和多系统萎缩。新出现的证据表明，α-突触核蛋白与各种细胞途径相互作用，包括线粒体功能障碍、氧化应激和神经炎症，这导致神经元细胞死亡。此外，α-突触核蛋白通过类朊病毒机制参与神经退行性过程的传播，其中错误折叠的蛋白质在相邻神经元中诱导类似的构象变化。了解 α-突触核蛋白在神经退行性变中的多方面作用，不仅有助于获得更多关于这些疾病病理生理学的知识，还突出了潜在的生物标志物和治疗靶点，以干预α-突触核蛋白病。在这篇综述中，我们总结了α-突触核蛋白导致神经退行性过程的机制，重点介绍了其错误折叠、寡聚化以及形成不溶性纤维的形成，这些纤维形成特征性的路易体。此外，我们比较了α-突触核蛋白物种在诊断和区分某些神经退行性疾病方面的潜在价值。
