Saleem Suraiya
Stem Cell and Molecular Biology Laboratory Bhupat & Jyoti Mehta School of Biosciences, Department of Biotechnology, Indian Institute of Technology, Madras, Chennai 600 036, Tamil Nadu, India.
Neuroscience. 2021 Aug 10;469:162-174. doi: 10.1016/j.neuroscience.2021.06.023. Epub 2021 Jun 21.
The progression of neurodegenerative disorders is mainly characterized by immense neuron loss and death of glial cells. The mechanisms which are active and regulate neuronal cell death are namely necrosis, necroptosis, autophagy and apoptosis. These death paradigms are governed by a set of molecular determinants that are pivotal in their performance and also exhibit remarkable overlapping functional pathways. A large number of such molecules have been demonstrated to be involved in the switching of death paradigms in various neurodegenerative diseases. In this review, we discuss various molecules and the concurrent crosstalk mediated by them. According to our present knowledge and research in neurodegeneration, molecules like Atg1, Beclin1, LC3, p53, TRB3, RIPK1 play switching roles toggling from one death mechanism to another. In addition, the review also focuses on the exorbitant number of newer molecules with the potential to cross communicate between death pathways and create a complex cell death scenario. This review highlights recent studies on the inter-dependent regulation of cell death paradigms in neurodegeneration, mediated by cross-communication between pathways. This will help in identifying potential targets for therapeutic intervention in neurodegenerative diseases.
神经退行性疾病的进展主要特征为大量神经元丧失和神经胶质细胞死亡。活跃并调节神经元细胞死亡的机制包括坏死、坏死性凋亡、自噬和凋亡。这些死亡模式由一组分子决定因素控制,这些因素在其发挥作用过程中至关重要,并且还呈现出显著的重叠功能途径。大量此类分子已被证明参与各种神经退行性疾病中死亡模式的转换。在本综述中,我们讨论了各种分子以及它们介导的同时发生的相互作用。根据我们目前对神经退行性变的认识和研究,诸如自噬相关蛋白1(Atg1)、贝林蛋白1(Beclin1)、微管相关蛋白1轻链3(LC3)、抑癌基因p53、 tribbles 同源物3(TRB3)、受体相互作用蛋白激酶1(RIPK1)等分子在从一种死亡机制切换到另一种死亡机制中发挥着作用。此外,本综述还关注了大量有潜力在死亡途径之间交叉通讯并产生复杂细胞死亡情况的新分子。本综述强调了近期关于神经退行性变中细胞死亡模式相互依赖调节的研究,这种调节由途径之间的交叉通讯介导。这将有助于确定神经退行性疾病治疗干预的潜在靶点。