Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)- Hyderabad, Balanagar, India.
CNS Neurol Disord Drug Targets. 2018;17(9):696-705. doi: 10.2174/1871527317666180816100203.
BACKGROUND & OBJECTIVE: Cellular physiology and energy metabolism are maintained by the constant supply of energy furnished by the powerhouses of the cell called mitochondria. Cellular homeostasis depends on the timely clearance of damaged cellular organelles and proteins via pathways including autophagy. Mitochondria and mitochondrial autophagy play a vital role in cellular health and failure of these pathways can have a devastating effect on cellular homeostasis. Amongst the various cell types, neuronal cells are more vulnerable to bioenergetic depletion since most of their functions critically depend on the availability of energy derived from mitochondrial metabolism, thus making neurodegenerative disorders an obstinate issue. Research in the past few decades has shown that these neurodegenerative disorders are associated with mitochondrial dysfunction and compromised mitophagy leading to accumulation of protein aggregates which ultimately culminate in neurodegeneration.
Thus, targeting mitochondria and autophagy-related proteins and enzymes in neurodegenerative disorders may open the avenues for potential targets for discovering effective therapies. Here, we review the involvement of mitochondrial and autophagy dysfunction in neurodegenerative disorders specifically focusing on Alzheimer's, Parkinson's and Huntington's disease.
细胞生理学和能量代谢依赖于细胞的“能量工厂”线粒体提供的持续能量供应来维持。细胞内稳态依赖于通过自噬等途径及时清除受损的细胞细胞器和蛋白质。线粒体和线粒体自噬在细胞健康中起着至关重要的作用,这些途径的失败会对细胞内稳态产生毁灭性的影响。在各种细胞类型中,神经元细胞对能量耗竭更为敏感,因为它们的大多数功能都严重依赖于线粒体代谢产生的能量,因此使神经退行性疾病成为一个顽固的问题。过去几十年的研究表明,这些神经退行性疾病与线粒体功能障碍和自噬受损有关,导致蛋白质聚集体的积累,最终导致神经退行性变。
因此,针对神经退行性疾病中的线粒体和自噬相关蛋白和酶可能为发现有效治疗方法提供潜在的靶点。在这里,我们综述了线粒体和自噬功能障碍在神经退行性疾病中的作用,特别是针对阿尔茨海默病、帕金森病和亨廷顿病。