Molecular Mechanisms of Cellular Senescence in Neurodegenerative Diseases

Neurodegenerative diseases, such as Alzheimer's and Parkinson's, are characterized by several patho-logical features, including selective neuronal loss, aggregation of specific proteins, and chronic inflamma-tion. 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 senes-cence is a cell state or fate in response to stimuli. It is typically associated with a series of changes in cel-lular 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 neurodegen-erative 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.(c) 2023 Elsevier Ltd. All rights reserved.