Department of Anatomy, Konkuk University, Seoul 05029, Republic of Korea; IBST, Konkuk University, Seoul 05029, Republic of Korea.
Department of Anatomy, Konkuk University, Seoul 05029, Republic of Korea; IBST, Konkuk University, Seoul 05029, Republic of Korea.
J Mol Biol. 2023 Jun 15;435(12):168114. doi: 10.1016/j.jmb.2023.168114. Epub 2023 Apr 20.
Neurodegenerative diseases, such as Alzheimer's and Parkinson's, are characterized by several pathological features, including selective neuronal loss, aggregation of specific proteins, and chronic inflammation. Aging is the most critical risk factor of these disorders. However, the mechanism by which aging contributes to the pathogenesis of neurodegenerative diseases is not clearly understood. Cellular senescence is a cell state or fate in response to stimuli. It is typically associated with a series of changes in cellular phenotypes such as abnormal cellular metabolism and proteostasis, reactive oxygen species (ROS) production, and increased secretion of certain molecules via senescence-associated secretory phenotype (SASP). In this review, we discuss how cellular senescence contributes to brain aging and neurodegenerative diseases, and the relationship between protein aggregation and cellular senescence. Finally, we discuss the potential of senescence modifiers and senolytics in the treatment of neurodegenerative diseases.
神经退行性疾病，如阿尔茨海默病和帕金森病，其特征是存在多种病理特征，包括选择性神经元丧失、特定蛋白质聚集以及慢性炎症。衰老时这些疾病的最重要的危险因素。然而，衰老导致神经退行性疾病发病机制的机制尚不清楚。细胞衰老（cellular senescence）是细胞对刺激的一种状态或命运。它通常与细胞表型的一系列变化相关，例如异常的细胞代谢和蛋白稳态、活性氧（ROS）产生，以及通过衰老相关分泌表型（SASP）增加某些分子的分泌。在这篇综述中，我们讨论了细胞衰老如何导致大脑衰老和神经退行性疾病，以及蛋白聚集与细胞衰老之间的关系。最后，我们讨论了衰老修饰剂和衰老细胞清除剂在治疗神经退行性疾病中的潜力。
