Abstract:
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.
摘要:
神经退行性疾病,比如阿尔茨海默氏症和帕金森氏症,有几个病理特征,包括选择性神经元丢失,特定蛋白质的聚集,慢性炎症。衰老是这些疾病最关键的危险因素。然而,衰老导致神经退行性疾病发病的机制尚不清楚。细胞衰老是响应刺激的细胞状态或命运。它通常与细胞表型的一系列变化有关,例如异常的细胞代谢和蛋白质停滞,活性氧(ROS)的产生,并通过衰老相关分泌表型(SASP)增加某些分子的分泌。在这次审查中,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,蛋白质聚集与细胞衰老的关系。最后,我们讨论了衰老调节剂和衰老剂在治疗神经退行性疾病中的潜力。