Biological Engineering Discipline, Indian Institute of Technology Gandhinagar, Palaj, 382355, Gujarat, India.
Biological Engineering Discipline, Indian Institute of Technology Gandhinagar, Palaj, 382355, Gujarat, India; Center for Biomedical Engineering Discipline, Indian Institute of Technology Gandhinagar, Palaj, 382355, Gujarat, India.
Biochimie. 2022 Jan;192:38-50. doi: 10.1016/j.biochi.2021.09.012. Epub 2021 Sep 25.
Parkinson's disease is the second most prevalent neurodegenerative disease. The loss of dopaminergic neurons in the substantia nigra is one of the pathological hallmarks of PD. PD also belongs to the class of neurodegenerative disease known as 'Synucleinopathies' as α-synuclein is responsible for disease development. The presence of aggregated α-synuclein associated with other proteins found in the Lewy bodies and Lewy neurites in the substantia nigra and other regions of the brain including locus ceruleus, dorsal vagal nucleus, nucleus basalis of Meynert and cerebral cortex is one of the central events for PD development. The complete biological function of α-synuclein is still debated. Besides its ability to propagate, it undergoes various post-translational modifications which play a paramount role in PD development and progression. Also, the aggregation of α-synuclein is modulated by various post-translational modifications. Here, we present a summary of multiple PTMs involved in the modulation of α-synuclein directly or indirectly and to identify their neuroprotective or neurotoxic roles, which might act as potential therapeutic targets for Parkinson's disease.
帕金森病是第二大常见的神经退行性疾病。黑质中多巴胺能神经元的丧失是 PD 的病理标志之一。PD 也属于被称为“突触核蛋白病”的神经退行性疾病类别，因为α-突触核蛋白负责疾病的发展。聚集的α-突触核蛋白与路易体和路易神经突中发现的其他蛋白质相关联，这些结构存在于黑质和大脑的其他区域，包括蓝斑、迷走神经背核、Meynert 基底核和大脑皮层，这是 PD 发展的核心事件之一。α-突触核蛋白的完整生物学功能仍存在争议。除了能够传播之外，它还经历了各种翻译后修饰，这些修饰在 PD 的发展和进展中起着至关重要的作用。此外，α-突触核蛋白的聚集受到多种翻译后修饰的调节。在这里，我们总结了直接或间接参与调节α-突触核蛋白的多种 PTM，并确定了它们的神经保护或神经毒性作用，这些作用可能成为帕金森病的潜在治疗靶点。
