Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer’s-like changes

Gupta, Amit; Bisht, Bharti; Dey, Chinmoy Sankar

doi:10.1016/j.neuropharm.2011.01.033

Cited by 260 publications

(169 citation statements)

References 61 publications

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“…While initial reports indicate that metformin increases the levels of brain Aβ by upregulating β-site APP cleaving enzyme 1 (BACE1) [125], some studies show that metformin attenuated AD-like changes and also reduced tau phosphorylation [126][127][128].…”

Section: Anti-diabetes Drugsmentioning

confidence: 99%

Drug Repositioning Approaches for the Discovery of New Therapeutics for Alzheimer's Disease

Kim

2015

Neurotherapeutics

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Summary Alzheimer's disease (AD) is the most common cause of dementia and represents one of the highest unmet needs in medicine today. Drug development efforts for AD have been encumbered by largely unsuccessful clinical trials in the last decade. Drug repositioning, a process of discovering a new therapeutic use for existing drugs or drug candidates, is an attractive and timely drug development strategy especially for AD. Compared with traditional de novo drug development, time and cost are reduced as the safety and pharmacokinetic properties of most repositioning candidates have already been determined. A majority of drug repositioning efforts for AD have been based on positive clinical or epidemiological observations or in vivo efficacy found in mouse models of AD. More systematic, multidisciplinary approaches will further facilitate drug repositioning for AD. Some experimental approaches include unbiased phenotypic screening using the library of available drug collections in physiologically relevant model systems (e.g. stem cell-derived neurons or glial cells), computational prediction and selection approaches that leverage the accumulating data resulting from RNA expression profiles, and genome-wide association studies. This review will summarize several notable strategies and representative examples of drug repositioning for AD.

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Section: Anti-diabetes Drugsmentioning

confidence: 99%

Drug Repositioning Approaches for the Discovery of New Therapeutics for Alzheimer's Disease

Kim

2015

Neurotherapeutics

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“…Recent studies proposed controversial evidences about metformin action including for or against AD. In one way metformin improves insulin resistance in the brain in line with other parts of the body and does not influence higher hyperinsulinemia [48]. In other way there are still evidences that condemn metformin for increasing Aβ generation and secretion that can have potential side-effects in accelerating clinical manifestation of AD among patients affected by type-2 diabetes [49].…”

Section: Discussionmentioning

confidence: 99%

Cognitive Impairment in Type 2 Diabetic Patients Treated with Metformin in Comparison with those Taking Glibenclamide

M¹,

Siavash²,

Ki³

et al. 2014

JNSK

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“…In addition, metformin has been shown to inhibit mammalian target of rapamycin complex 1signaling and increase longevity in mice [32] . In an in-vitro study of neuronal insulin-resistant model with hallmark AD-like changes, treatment with metformin alleviates neuronal insulin resistance and prevents the appearance of molecular and pathological characteristics of AD [33] . The administration of both insulin and metformin can provide significant neuroprotection against AD pathology, including β-amyloid neuritic plaques and down-regulation of the insulin receptor, thus improving cognitive function.…”

Section: Metforminmentioning

confidence: 99%

Fight against Glucose Rescues Age-Related Cognitive Decline

Tong

Chen

2016

Neurosci Commun

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Aging is commonly associated with dysfunctions of various systems, especially the cognitive decline that seriously diminishes the independence and life quality of old individuals. Exploring the approaches for maintaining a healthy brain is now a critical public health concern. Calorie restriction (CR) has been known to extend longevity, promote metabolic health, and delay the progress of aging and the risk of age-related diseases, such as type 2 diabetes and Alzheimer's disease (AD). Studies have shown that CR improves the insulin sensitivity. Moreover, defected insulin signaling in individuals with or without diabetes is related to a higher risk of age-related cognitive deficits or AD. Evidences suggest that treatment of diabetes mimics the activity of CR, modulating the metabolism of glucose and lipid and the function of insulin system, thus may has the anti-aging potential. In this paper, we reviewed the laboratory experiment and clinical data that focused on the protective role of CR, and that investigated the effect of several types of common agents for diabetes treatment on aging or cognitive ability. The progress in recent years inspires researchers to explore the mechanisms of age-related cognitive decline, and search for safe and effective therapeutic strategies. In the future, more high-quality studies are required to optimize the application of CR or diabetes therapies on the prevention or treatment of brain aging.

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Peripheral insulin-sensitizer drug metformin ameliorates neuronal insulin resistance and Alzheimer’s-like changes

Cited by 260 publications

References 61 publications

Drug Repositioning Approaches for the Discovery of New Therapeutics for Alzheimer's Disease

Drug Repositioning Approaches for the Discovery of New Therapeutics for Alzheimer's Disease

Cognitive Impairment in Type 2 Diabetic Patients Treated with Metformin in Comparison with those Taking Glibenclamide

Fight against Glucose Rescues Age-Related Cognitive Decline

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