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Deciphering the Role of WNT Signaling in Metabolic Syndrome–Linked Alzheimer’s Disease

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Abstract

It has been well established in recent research that there is a strong correlation between metabolic syndrome (MetS) and Alzheimer’s disease (AD). However, the knowledge of exact mechanistic behind this association remains elusive. It has been reported in recent studies that inflammation and hypercoagulation are pivotal to the pathophysiology of MetS-induced AD. It is rather captivating that aberrant Wnt signaling pathway has been found to be implicated in each of the four conditions, i.e., inflammation, hypercoagulation, MetS, and AD. Deregulation of Wnt signaling has been affiliated with numerous brain pathologies, including Alzheimer’s disease and insulin resistance. In recent past, it has been proposed that the Wnt pathway can act as a central integrator of metabolic signals from peripheral organs to the brain, which would constitute a unique character for Wnt signaling in glucose metabolism. The review educates in what way distinct components of Wnt signaling impact effector mediators of inflammation, hypercoagulation, which in turn decelerate the progression of AD in MetS. Furthermore, components of Wnt signaling, namely, Wnt3a and GSK-3β, interlink MetS and AD. The review opines a contemporary hypothesis that Wnt signaling is implicated in the pathogenesis of MetS-induced AD via impacting inflammation and coagulation. Hence, targeting Wnt signaling could be a novel approach to halt the progression of MetS-linked AD.

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Ali, A., Ali, A., Ahmad, W. et al. Deciphering the Role of WNT Signaling in Metabolic Syndrome–Linked Alzheimer’s Disease. Mol Neurobiol 57, 302–314 (2020). https://doi.org/10.1007/s12035-019-01700-y

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