Cellular and metabolic alterations in the hippocampus caused by insulin signalling dysfunction and its association with cognitive impairment during aging and Alzheimer's disease: studies in animal models.
A growing body of animal and epidemiological studies suggest that metabolic diseases such as obesity, insulin resistance, metabolic syndrome and type 2 diabetes mellitus are associated with the development of cognitive impairment, dementia and Alzheimer's disease, particularly in aging. Several lines of evidence suggest that insulin signalling dysfunction produces these metabolic alterations and underlie the development of these neurodegenerative diseases. In this article, we address normal insulin function in the synapse; we review and discuss the physiopathological hallmarks of synaptic insulin signalling dysfunction associated with metabolic alterations. Additionally, we describe and review the major animal models of obesity, insulin resistance, metabolic syndrome and type 2 diabetes mellitus. The comprehensive knowledge of the molecular mechanisms behind the association of metabolic alterations and cognitive impairment could facilitate the early detection of neurodegenerative diseases in patients with metabolic alterations, with treatment that focus on neuroprotection. It could also help in the development of metabolic-based therapies and drugs for using in dementia and Alzheimer's disease patients to alleviate their symptoms in a more efficient and comprehensive way.
Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, DF, Mexico.
Erika
E
Calvo-Ochoa
Clorinda
C
Arias
D000544:Alzheimer Disease / Q000150:complications* / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D009765:Obesity / Q000150:complications / Q000453:epidemiology; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
D007328:Insulin
Alzheimer's disease; cognitive decline; diabetes; hippocampal dysfunction; insulin resistance; obesity