The cGAS–STING Pathway in Dementia: An Emerging Mechanism of Neuroinflammation

Dementia, characterized by a progressive decline in cognitive function, is a growing global health concern due to the aging population. It affects memory, executive function, language, and other cognitive capacities, significantly impairing daily life. Despite the growing burden, effective preventive and therapeutic strategies remain elusive, emphasizing the urgent need for novel interventions. Recent advances underscore the pivotal role of neuroinflammation in dementia pathogenesis, particularly in Alzheimer's disease (AD). Chronic activation of immune cells within the central nervous system, such as microglia transition from a homeostatic to a pro-inflammatory state called Disease-associated microglia status 1 and 2 (DAM1 or DAM2), exacerbates neurodegeneration, creating a self-perpetuating cycle of inflammation and cognitive decline. This review focuses on emerging research exploring the cGAS-STING pathway’s role in dementia, examining its potential as a diagnostic and therapeutic target. The cGAS-STING pathway, integral to innate immune responses, may contribute to the chronic neuroinflammation seen in neurodegenerative diseases. By targeting this pathway, new strategies could mitigate the inflammatory processes that drive neuronal loss, offering a promising avenue for therapeutic development in dementia.