Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México, DF, Mexico.
Diabetes Metab Res Rev. 2015 Jan;31(1):1-13. doi: 10.1002/dmrr.2531.
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.
越来越多的动物和流行病学研究表明，代谢疾病（如肥胖、胰岛素抵抗、代谢综合征和 2 型糖尿病）与认知障碍、痴呆和阿尔茨海默病的发展有关，特别是在衰老过程中。有几条证据表明胰岛素信号功能障碍会产生这些代谢改变，并为这些神经退行性疾病的发展提供基础。在本文中，我们将讨论突触中正常的胰岛素功能；我们回顾和讨论了与代谢改变相关的突触胰岛素信号功能障碍的病理生理学特征。此外，我们还描述和回顾了肥胖、胰岛素抵抗、代谢综合征和 2 型糖尿病的主要动物模型。对代谢改变和认知障碍之间关联的分子机制的全面了解，可以促进在代谢改变的患者中早期发现神经退行性疾病，并进行以神经保护为重点的治疗。它还有助于开发基于代谢的疗法和药物，用于痴呆和阿尔茨海默病患者，以更有效和全面的方式缓解其症状。
