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Molecular and Biochemical Pathways Encompassing Diabetes Mellitus and Dementia

期刊

CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
卷 21, 期 7, 页码 542-556

出版社

BENTHAM SCIENCE PUBL
DOI: 10.2174/1871527320666211110115257

关键词

Alzheimer's disease; diabetes mellitus; insulin resistance; metabolic disorder; glycogen synthase kinase 3 beta (GSK3 beta); forkhead box o (FOXO)

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Diabetes and dementia are closely related, with diabetes patients being more susceptible to cognitive impairment and Alzheimer's disease, and Alzheimer's patients often exhibiting symptoms of diabetes. Insulin plays a crucial role in this vicious cycle, making anti-diabetic drugs beneficial in Alzheimer's treatment. Developing more insulin-targeting molecules and diagnosing impaired insulin signaling and cognitive decline early are important for preventing disease progression.
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.

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