Targeting Insulin Signaling for the Treatment of Alzheimer's Disease

Title:Targeting Insulin Signaling for the Treatment of Alzheimer's Disease

Volume: 16 Issue: 5

Author(s): Yanxing Chen, Jianfang Zhang, Baorong Zhang and Cheng-Xin Gong

Affiliation:

Keywords: Alzheimer's disease, Anti-diabetic drugs, Brain insulin signaling, Dipeptidyl peptidase IV inhibitors, Glucose metabolism, Metformin, Incretins, Thiazolidinediones.

Abstract: Sporadic Alzheimer's disease (AD) is caused by multiple etiological factors, among which impaired brain insulin signaling and decreased brain glucose metabolism are important metabolic factors. Contrary to previous belief that insulin would not act in the brain, studies in the last three decades have proven important roles of insulin and insulin signaling in various biological functions in the brain. Impaired brain insulin signaling or brain insulin resistance and its role in the molecular pathogenesis of sporadic AD have been demonstrated. Thus, targeting brain insulin signaling for the treatment of cognitive impairment and AD has now attracted much attention in the field of AD drug discovery. This article reviews recent studies that target brain insulin signaling, especially those investigations on intranasal insulin administration and drugs that improve insulin sensitivity, including incretins, dipeptidyl peptidase IV inhibitors, thiazolidinediones, and metformin. These drugs have been previously approved for the treatment of diabetes mellitus, which could expedite their development for the treatment of AD. Although larger clinical trials are needed for validating their efficacy for the treatment of cognitive impairment and AD, results of animal studies and clinical trials available to date are encouraging.

Cite this article as:

Chen Yanxing, Zhang Jianfang, Zhang Baorong and Gong Cheng-Xin, Targeting Insulin Signaling for the Treatment of Alzheimer's Disease, Current Topics in Medicinal Chemistry 2016; 16 (5) . https://dx.doi.org/10.2174/1568026615666150813142423