Kapil Lakshay, Kumar Vishal, Kaur Simranjit, Sharma Deepali, Singh Charan, Singh Arti
Department of Pharmacology, ISF College of Pharmacy, Moga-142001, Punjab India.
Affiliated to IK Gujral Punjab Technical University, Jalandhar, Punjab, India.
CNS Neurol Disord Drug Targets. 2024;23(3):367-383. doi: 10.2174/1871527322666230327092855.
Autophagy is a self-destructive cellular process that removes essential metabolites and waste from inside the cell to maintain cellular health. Mitophagy is the process by which autophagy causes disruption inside mitochondria and the total removal of damaged or stressed mitochondria, hence enhancing cellular health. The mitochondria are the powerhouses of the cell, performing essential functions such as ATP (adenosine triphosphate) generation, metabolism, Ca buffering, and signal transduction. Many different mechanisms, including endosomal and autophagosomal transport, bring these substrates to lysosomes for processing. Autophagy and endocytic processes each have distinct compartments, and they interact dynamically with one another to complete digestion. Since mitophagy is essential for maintaining cellular health and using genetics, cell biology, and proteomics techniques, it is necessary to understand its beginning, particularly in ubiquitin and receptor-dependent signalling in injured mitochondria. Despite their similar symptoms and emerging genetic foundations, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) have all been linked to abnormalities in autophagy and endolysosomal pathways associated with neuronal dysfunction. Mitophagy is responsible for normal mitochondrial turnover and, under certain physiological or pathological situations, may drive the elimination of faulty mitochondria. Due to their high energy requirements and post-mitotic origin, neurons are especially susceptible to autophagic and mitochondrial malfunction. This article focused on the importance of autophagy and mitophagy in neurodegenerative illnesses and how they might be used to create novel therapeutic approaches for treating a wide range of neurological disorders.
自噬是一种自我破坏性的细胞过程,可从细胞内部清除必需的代谢物和废物,以维持细胞健康。线粒体自噬是自噬导致线粒体内破坏并完全清除受损或应激线粒体的过程,从而增强细胞健康。线粒体是细胞的动力源,执行诸如产生三磷酸腺苷(ATP)、代谢、钙缓冲和信号转导等重要功能。许多不同的机制,包括内体和自噬体运输,将这些底物带到溶酶体进行处理。自噬和内吞过程各有不同的区室,它们相互动态作用以完成消化。由于线粒体自噬对于维持细胞健康至关重要,并且利用遗传学、细胞生物学和蛋白质组学技术,有必要了解其起始过程,特别是在受损线粒体中的泛素和受体依赖性信号传导方面。尽管阿尔茨海默病(AD)、帕金森病(PD)、亨廷顿病(HD)和肌萎缩侧索硬化症(ALS)有相似的症状和新出现的遗传基础,但它们都与自噬和内溶酶体途径异常以及神经元功能障碍有关。线粒体自噬负责正常的线粒体更新,并且在某些生理或病理情况下,可能促使有缺陷的线粒体被清除。由于神经元对能量需求高且起源于有丝分裂后,它们特别容易受到自噬和线粒体功能障碍的影响。本文重点论述了自噬和线粒体自噬在神经退行性疾病中的重要性,以及它们如何可用于开发治疗多种神经疾病的新治疗方法。