Smriti Gupta, Nitin Kumar Singhal, Subramaniam Ganesh and Rajat Sandhir* Pages 1 - 13 ( 13 )
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.
Alzheimer’s disease, Amyloid beta, GSK3β, Insulin, Insulin degrading enzyme, miRNA, Type 3 Diabetes
Department of Biochemistry, Panjab University, Chandigarh, National Agri-Food Biotechnology Institute, Sector 81, S.A.S. Nagar, Mohali, Punjab 140306, Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016, Department of Biochemistry, Panjab University, Chandigarh