Title:Molecular and Biochemical Pathways Encompassing Diabetes Mellitus
and Dementia
Volume: 21
Issue: 7
Author(s): Tapan Behl*, Arpita Arora, Aayush Sehgal, Sukhbir Singh, Neelam Sharma, Saurabh Bhatia, Ahmed Al-Harrasi, Simona Bungau and Ebrahim Mostafavi*
Affiliation:
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
- Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA
- Department of Medicine, Stanford University
School of Medicine, Stanford, CA, USA
Keywords:
Alzheimer’s disease, diabetes mellitus, insulin resistance, metabolic disorder, glycogen synthase kinase 3 beta (GSK3β), forkhead box o (FOXO).
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.
