Laboratory of Translational Medicine and Nanotherapeutics, Department of Human Genetics and Molecular Medicine, School of Health Sciences, Central University of Punjab, Bathinda, India.
Department of Medical Lab Technology, University Institute of Applied Health Sciences, Chandigarh University, Mohali, India.
Life Sci. 2022 Dec 15;311(Pt A):121153. doi: 10.1016/j.lfs.2022.121153. Epub 2022 Nov 4.
The high prevalence of neurodegenerative diseases has become a major public health challenge and is associated with a tremendous burden on individuals, society and federal governments worldwide. Protein misfolding and aggregation are the major pathological hallmarks of several neurodegenerative disorders. The cells have evolved several regulatory mechanisms to deal with aberrant protein folding, namely the classical ubiquitin pathway, where ubiquitination of protein aggregates marks their degradation via lysosome and the novel autophagy or mitophagy pathways. Autophagy is a catabolic process in eukaryotic cells that allows the lysosome to recycle the cell's own contents, such as organelles and proteins, known as autophagic cargo. Their most significant role is to keep cells alive in distressed situations. Mitophagy is also crucial for reducing abnormal protein aggregation and increasing organelle clearance and partly accounts for maintaining cellular homeostasis. Furthermore, substantial data indicate that any disruption in these homeostatic mechanisms leads to the emergence of several age-associated metabolic and neurodegenerative diseases. So, targeting autophagy and mitophagy might be a potential therapeutic strategy for a variety of health conditions.
神经退行性疾病的高发率已成为一个主要的公共卫生挑战,给全世界的个人、社会和联邦政府带来了巨大的负担。蛋白质错误折叠和聚集是几种神经退行性疾病的主要病理特征。细胞已经进化出几种调节机制来应对异常的蛋白质折叠,即经典的泛素途径,其中蛋白质聚集体的泛素化标记它们通过溶酶体降解,以及新的自噬或线粒体自噬途径。自噬是真核细胞中的一种分解代谢过程,允许溶酶体回收细胞自身的内容物,如细胞器和蛋白质,称为自噬货物。它们最重要的作用是在困境中使细胞存活。线粒体自噬对于减少异常蛋白质聚集和增加细胞器清除也至关重要,部分原因是维持细胞内环境稳定。此外,大量数据表明,这些动态平衡机制的任何破坏都会导致多种与年龄相关的代谢和神经退行性疾病的出现。因此,靶向自噬和线粒体自噬可能是多种健康状况的潜在治疗策略。