Background & Objective: Type 3 diabetes (T3D) is chronic insulin resistant state of brain
which shares pathology with sporadic Alzheimer’s disease (sAD). Insulin signaling is a highly conserved
pathway in the living systems that orchestrate cell growth, repair, maintenance, energy homeostasis
and reproduction. Although insulin is primarily studied as a key molecule in diabetes mellitus,
its role has recently been implicated in the development of Alzheimer’s disease (AD). Severe complications
in brain of diabetic patients and metabolically compromised status is evident in brain of AD
patients. Underlying shared pathology of two disorders draws a trajectory from peripheral insulin resistance
to insulin unresponsiveness in the central nervous system (CNS). As insulin has a pivotal role
in AD, it is not an overreach to address diabetic condition in AD brain as T3D. Insulin signaling is
indispensable to nervous system and it is vital for neuronal growth, repair, and maintenance of
chemical milieu at synapses. Downstream mediators of insulin signaling pathway work as a regulatory
hub for aggregation and clearance of unfolded proteins like Aβ and tau.
Conclusion: In this review, we discuss the regulatory roles of insulin as a pivotal molecule in brain
with the understanding of defective insulin signaling as a key pathological mechanism in sAD. This
article also highlights ongoing trials of targeting insulin signaling as a therapeutic manifestation to
treat diabetic condition in brain.
Keywords: Alzheimer’s disease, Amyloid beta, GSK3β, Insulin, Insulin degrading enzyme, miRNA, Type 3 Diabetes.
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