Insulin resistance and bioenergetic manifestations: Targets and approaches in Alzheimer's disease

Abstract

Aim: Insulin has a well-established role in cognition, neuronal detoxification and synaptic plasticity. Insulin transduction affect neurotransmitter functions, influence bioenergetics and regulate neuronal survival through regulating glucose energy metabolism and downward pathways. Methods: A systematic literature review of PubMed, Medline, Bentham, Scopus and EMBASE (Elsevier) databases was carried out with the help of the keywords like "Alzheimer's disease; Hypometabolism; Oxidative stress; energy failure in AD, Insulin; Insulin resistance; Bioenergetics" till June 2020. The review was conducted using the above keywords to collect the latest articles and to understand the nature of the extensive work carried out on insulin resistance and bioenergetic manifestations in Alzheimer's disease. Key findings: The article sheds light on insulin resistance mediated hypometabolic state on pathological progression of AD. The disrupted insulin signaling has pathological outcome in form of disturbed glucose homeostasis, altered bioenergetic state which increases build-up of senile plaques (A?), neurofibrillary tangles (?), decline in transportation of glucose and activation of inflammatory pathways. The mechanistic link of insulin resistant state with therapeutically explorable potential transduction pathways is the focus of the reviewed work. Significance: The present work opines that the mechanism by which the insulin resistance mediates dysregulation of bioenergetics and progresses to neurodegenerative state holds the tangible potential to succeed in the development of novel dementia therapies. Further, hypometabolic complications and altered insulin signaling may be explored as a mechanistic relation between bioenergetic deficits and AD.