Unveiling the role of astrogliosis in Alzheimer's disease Pathology: Insights into mechanisms and therapeutic approaches

Alzheimer's disease (AD) is one of the most debilitating age-related disorders that affect people globally. It impacts social and cognitive behavior of the individual and is characterized by phosphorylated tau and A beta accumulation. Astrocytes maintain a quiescent, anti-inflammatory state on anatomical level, expressing few cytokines and exhibit phagocytic activity to remove misfolded proteins. But in AD, in response to specific stimuli, astrocytes overstimulate their phagocytic character with overexpressing cytokine gene modules. Upon interaction with generated A beta and neurofibrillary tangle, astrocytes that are continuously activated release a large number of inflammatory cytokines. This cytokine storm leads to neuroinflammation which is also one of the recognizable features of AD. Astrogliosis eventually promotes cholinergic dysfunction, calcium imbalance, oxidative stress and excitotoxicity. Furthermore, C5aR1, Lcn2/, BDNF/TrkB and PPAR alpha/TFEB signaling dysregulation has a major impact on the disease progression. This review clarifies numerous ways that lead to astrogliosis, which is stimulated by a variety of processes that exacerbate AD pathology and make it a suitable target for AD treatment. Drugs under clinical and preclinical investigations that target several pathways managing astrogliosis and are efficacious in ameliorating the pathology of the disease are also included in this study. D-ALA2GIP, TRAM-34, Genistein, L-serine, MW150 and XPro1595 are examples of few drugs targeting astrogliosis. Therefore, this study may aid in the development of a potent therapeutic agent for ameliorating astrogliosis mediated AD progression.