Traversing Through the Trajectory of Pathogenic Astrocytes in Alzheimer’s Disease

Alzheimer’s disease (AD) is a prevalent and debilitating neurological condition with no curable therapies in the pipeline. Alzheimer’s disease-related neurodegeneration negatively influences various brain cells, including astrocytes, neurons, and microglia. Interactions between healthy neural cell types and AD hallmarks: Aβ plaques and tau fibril deposits have been shown to produce detrimen-tal cellular stresses and deterioration in brain functions. Astrocytes help to regulate nutritional balance, cerebral blood flow, tissue healing, and the blood–brain barrier. They engage in the CNS’sinflammatory/immune responses. Evidence also suggests that astrocytes have neuroprotective and neurotoxic effects based on the disease stage and microenvironment. Changes in astrocyte function have been observed in individuals with early-onset Alzheimer’s disease, displaying disproportions in gliotransmission, neurotransmitter homeostasis, astroglial atrophy, disruptions in synaptic associations, neuroinflammation, and neurodegeneration. Moreover, the presence of Aβ plaques appears to impact astrocytes, affecting calcium levels and pro-inflammatory activity via RAGE-NF-kB pathway. The conventional treatment approaches for AD-related neuropathology are not anticipated to be comprehensive. The rationale for this may be that AD treatment involves a therapeutic strategy to minimize its cascading recurrence, and most drugs are inefficient at developing effective responses. Hence, researchers are keen on exploring the roles of astrocytes and their molecular pathways to identify potent therapies in AD. This review pro-vides a broad approach, emphasizing the roles of astrocytes in healthy brains and their pathological changes in AD, as well as potential astrocyte-related therapy regimens. Novel strategies comprising astrocytes and aimed at alleviating oxidative stress and neuroinflammation in AD have also been presented.