Autophagy Dysfunction and its Link to Alzheimer’s Disease and Type II Diabetes Mellitus
CNS & Neurological Disorders - Drug Targets,
Cornelia M. Wilson, Amandine Magnaudeix, Catherine Yardin and Faraj TerroAffiliation:
Groupe de Neurobiologie Cellulaire- EA3842 Homeostasie cellulaire et pathologies, Universite de Limoges, Faculte de Medecine 2, rue du Dr Raymond Marcland, 87025 Limoges CEDEX, France.
AbstractEpidemiological data testifies the increasing incidence of Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM). Some associations were made between occidental lifestyle and development of these pathologies, moreover AD and T2DM are linked since each pathology is a causative risk factor for the other. Interestingly, autophagy, a catabolic pathway whose efficiency declines with age is importantly impaired in the affected tissues. Autophagy regulation is dependent of cell metabolic status and consequently on the 5’AMP-activated protein kinase (AMPK) and mammalian target of rapamycin signaling pathways. These pathways are altered with aging and molecular, pharmacological and physiological interventions increase lifespan in various organismal models and favours healthy aging diminishing the occurrence of age-related diseases such as diabetes, cancer, cardiovascular and neurodegenerative pathologies. Decreasing calorie intake has been known for a long time to have a beneficial effect on longevity and health. Some drug agonists of AMPK are known to mimic these effects such as metformin or resveratrol, a polyphenol extracted from plants and present in red wine, a component of the French paradox related diet. In this review, we present the epidemiological and pathogenesis links existing between AD and T2DM with an insight into the perturbations of the autophagic process highlighting the crucial role of the AMPK in development of age and metabolic related diseases. Hence, in a last part we will discuss the possible interventions susceptible to combat both T2DM and AD.
Aging, Alzheimer’s disease, 5’AMP-activated protein kinase, autophagy, mammalian target of rapamycin, type 2 diabetes.
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