Jiang Jinwen, Liu Yu, Wu Qihui
Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.
Front Neurosci. 2021 Nov 18;15:781722. doi: 10.3389/fnins.2021.781722. eCollection 2021.
Alzheimer's and Parkinson's diseases (AD and PD) are amongst top of the prevalent neurodegenerative disease. One-third of PD patients are diagnosed with dementia, a pre-symptom of AD, but the underlying mechanism is elusive. Amyloid beta (Aβ) and α-synuclein are two of the most investigated proteins, whose pathological aggregation and spreading are crucial to the pathogenesis of AD and PD, respectively. Transcriptomic studies of the mammalian central nervous system shed light on gene expression profiles at molecular levels, regarding the complexity of neuronal morphologies and electrophysiological inputs/outputs. In the last decade, the booming of the single-cell RNA sequencing technique helped to understand gene expression patterns, alternative splicing, novel transcripts, and signal pathways in the nervous system at single-cell levels, providing insight for molecular taxonomy and mechanistic targets of the degenerative nervous system. Here, we re-visited the cell-cell transmission mechanisms of Aβ and α-synuclein in mediating disease propagation, and summarized recent single-cell transcriptome sequencing from different perspectives and discussed its understanding of neurodegenerative diseases.
阿尔茨海默病和帕金森病（AD和PD）是最常见的神经退行性疾病。三分之一的帕金森病患者被诊断患有痴呆症，这是阿尔茨海默病的一种前驱症状，但其潜在机制尚不清楚。β-淀粉样蛋白（Aβ）和α-突触核蛋白是研究最多的两种蛋白质，它们的病理聚集和扩散分别对阿尔茨海默病和帕金森病的发病机制至关重要。哺乳动物中枢神经系统的转录组学研究揭示了分子水平上的基因表达谱，涉及神经元形态和电生理输入/输出的复杂性。在过去十年中，单细胞RNA测序技术的蓬勃发展有助于在单细胞水平上了解神经系统中的基因表达模式、可变剪接、新转录本和信号通路，为退行性神经系统的分子分类和机制靶点提供了见解。在这里，我们重新审视了Aβ和α-突触核蛋白在介导疾病传播中的细胞间传递机制，并从不同角度总结了最近的单细胞转录组测序，并讨论了其对神经退行性疾病的理解。
