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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Review Article

Molecular and Biochemical Pathways Encompassing Diabetes Mellitus and Dementia

(E-pub Ahead of Print)
Published on: 09 December, 2021
Author(s): Tapan Behl*, Arpita Arora, Aayush Sehgal, Sukhbir Singh, Neelam Sharma, Saurabh Bhatia, Ahmed Al-Harrasi, Simona Bungau and Ebrahim Mostafavi*

DOI: 10.2174/1871527320666211110115257

open access plus

Abstract

Diabetes mellitus is a major metabolic disorder that has now emerged as an epidemic, and it affects the brain through an array of pathways. Patients with diabetes mellitus can develop pathological changes in the brain, which eventually take the shape of mild cognitive impairment, which later progresses to Alzheimer’s disease. A number of preclinical and clinical studies have demonstrated this fact, and molecular pathways, such as amyloidogenesis, oxidative stress, inflammation, and impaired insulin signaling, are found to be identical in diabetes mellitus and dementia. However, the critical player involved in the vicious cycle of diabetes mellitus and dementia is insulin, whose signaling, when impaired in diabetes mellitus (both type 1 and 2), leads to a decline in cognition, although other pathways are also essential contributors. Moreover, it is not only the case that patients with diabetes mellitus indicate cognitive decline at a later stage, but many patients with Alzheimer’s disease also reflect symptoms of diabetes mellitus, thus creating a vicious cycle inculcating a web of complex molecular mechanisms and hence categorizing Alzheimer’s disease as ‘brain diabetes.’ Thus, it is practical to suggest that anti-diabetic drugs are beneficial in Alzheimer’s disease. However, only smaller trials have showcased positive outcomes mainly because of the late onset of therapy. Therefore, it is extremely important to develop more of such molecules that target insulin in patients with dementia along with such methods that diagnose impaired insulin signaling and the associated cognitive decline so that early therapy may be initiated and the progression of the disease can be prevented.

Keywords: Alzheimer’s disease, diabetes mellitus, insulin resistance, metabolic disorder, glycogen synthase kinase 3 beta (GSK3β), forkhead box o (FOXO).


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