The role of galanin/GALR2 signaling in the link between type 2 diabetes and Alzheimer's disease.

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are two major healthcare problems among the elderly worldwide. Several epidemiological studies suggest that T2DM is associated with an increased risk of developing AD, leading to cognitive decline and loss of behavioral abilities. Despite many studies probing into the insulin resistance that serves as a pivotal etiopathology link between T2DM and AD, the precise mechanism for this association of both diseases is still poorly understood. Emerging evidence suggests that galanin and galanin receptor 2 (GALR2) are broadly described in the early steps of T2DM and AD and play the crucial role in the intersection between both two diseases in preclinical models. The dysregulation of the galanin-GALR2 axis plays a major role in the development of both diseases based on animal and cellular studies and has emerged as a plausible molecular pathogenesis link between them. In this review article, we mainly summarize our and other recent studies to provide a new insight into the multivariate relationship among galanin-GALR2, T2DM and AD, highlighting the beneficial effect of galanin/GALR2 signaling on the comorbid state of both diseases in preclinical models, and explain the underlying molecular mechanism in T2DM and AD pathogenesis. These may strengthen our knowledge of the pathophysiology of AD and T2DM based on preclinical studies and provide helpful hints for future research, such as whether GALR2 agonists might be determined as a potential therapeutic approach to treat both conditions.