Abstract
Astrocytes are the largest group of glial cells in the brain and participate in several essential functions of the central nervous system (CNS). Disruption of their normal physiological function can lead to metabolism disequilibrium and the pathology of CNS. As an important mechanism of aging, cellular senescence has been considered as a primary inducing factor of age-associated neurodegenerative disorders. Senescent astrocytes showed decreased normal physiological function and increased secretion of senescence-associated secretory phenotype (SASP) factors, which contribute to Aβ accumulation, tau hyperphosphorylation, and the deposition of neurofibrillary tangles (NFTs) in Alzheimer’s disease (AD). Astrocyte senescence also leads to a number of detrimental effects, including induced glutamate excitotoxicity, impaired synaptic plasticity, neural stem cell loss, and blood–brain barrier (BBB) dysfunction. In this review article, we have summarized the growing findings regarding astrocyte senescence and its putative role in the pathologic progress of AD. Additionally, we also focus on the significance of targeting astrocyte senescence as a novel and feasible therapeutic approach for AD.
Highlights
Alzheimer’s disease (AD) is a chronic degenerative disorder of the brain related to progressive decline of memory and cognition (McGeer and McGeer, 2007; Long and Holtzman, 2019)
Senescent astrocytes exhibit permanent cell cycle arrest as well as other cell types, which is thought to be regulated by the p53/p21WAF1 and p16INK4A/pRB pathway (Evans et al, 2003; Bitto et al, 2010; Turnquist et al, 2019). p21WAF1 is namely the CIP/KIP (CDK interacting protein/kinase inhibitory protein) that is capable of inhibiting CDK2, but paradoxically, it is necessary for cell cycle progression (Hernandez-Segura et al, 2018)
This implies that astrocyte senescence associated with an increase in glial fibrillary acidic protein (GFAP) expression, which results in the upregulation of GFAP, may be a new biomarker of astrocyte senescence (Figure 1)
Summary
Alzheimer’s disease (AD) is a chronic degenerative disorder of the brain related to progressive decline of memory and cognition (McGeer and McGeer, 2007; Long and Holtzman, 2019). Astrocytes are the major glial cells and are vital for the normal physiological functions of the central nervous system (CNS) (Sofroniew and Vinters, 2010; Matias et al, 2019). They perform critical roles in regulation of homeostasis and metabolism of the neurons, mediating uptake and recycling. Transcriptome analysis of AD and the aged human brain showed neurons and other non-neuronal CNS cell types including astrocytes, microglia, and oligodendrocytes displayed senescence-associated phenotypes (Salminen et al, 2011; Bhat et al, 2012; Boccardi et al, 2015; Boisvert et al, 2018; Bussian et al, 2018; Zhang P. et al, 2019). Astrocytes have been shown to undergo cellular senescence in vitro and in vivo due to various stimuli and factors
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