The Role of Glial Cell Senescence in Alzheimer's Disease

Abstract

Glial cell senescence, characterized by the irreversible arrest of cell division and a pro-inflammatory secretory phenotype, has emerged as a critical player in the pathogenesis of Alzheimer's disease (ad). While much attention has been devoted to the role of neurons in ad, growing evidence suggests that glial cells, including astrocytes, microglia, and oligodendrocytes, contribute significantly to disease progression through senescence. In this review, we explore the molecular mechanisms underlying glial cell senescence in ad, focusing on the cellular signaling pathways, including DNA damage response and the accumulation of senescence-associated secretory phenotypes (SASP). We also examine how senescent glial cells exacerbate neuroinflammation, disrupt synaptic function, and promote neuronal death in ad. Moreover, we discuss emerging therapeutic strategies aimed at targeting glial cell senescence to mitigate the neurodegenerative processes in ad. By providing a comprehensive overview of current research on glial cell senescence in Alzheimer's disease, this review highlights its potential as a novel therapeutic target in the fight against ad.