Insulin Resistance and Neurodegeneration: Progress Towards the Development of New Therapeutics for Alzheimer's Disease.
Insulin Resistance and Neurodegeneration: Progress Towards the Development of New Therapeutics for Alzheimer's Disease.
复制标题
胰岛素抵抗和神经退行性：朝着为阿尔茨海默氏病开发新疗法的进展。
DOI：
10.1007/s40265-016-0674-0
复制
发表时间：
2017-01
期刊：
影响因子：
11.5
通讯作者：
de la Monte SM
中科院分区：
文献类型：
--
作者：
de la Monte SM
阿尔茨海默病（Alzheimer's disease，AD）是一种由脑胰岛素抵抗和缺乏引起的退行性代谢性疾病，与糖尿病、非酒精性脂肪肝和代谢综合征的分子、生化、病理生理和代谢功能障碍重叠。尽管过去几十年的大多数诊断和治疗方法都集中在淀粉样蛋白-β（Aβ42）和异常磷酸化的tau（其可能由脑胰岛素抵抗的后果引起）上，但更广泛的病理包括白色物质萎缩伴有髓原纤维丢失和脑白质疏松、非A β42微血管疾病、脂质代谢失调、线粒体功能障碍、星形胶质细胞增生、Aβ42蓄积不能解释神经炎症和突触丧失与营养不良性神经突生长的关系，但可以解释为胰岛素/IGF-1信号传导失调，伴随信号转导和基因表达受损。这篇综述涵盖了AD中各种各样的脑异常，并讨论了如何利用胰岛素，肠促胰岛素和胰岛素增敏剂来治疗不同阶段的神经退行性变。
Alzheimer’s disease (AD) should be regarded as a degenerative metabolic disease caused by brain insulin resistance and deficiency, and overlapping with the molecular, biochemical, pathophysiological, and metabolic dysfunctions occurring in diabetes mellitus, non-alcoholic fatty liver disease, and metabolic syndrome. Although most of the diagnostic and therapeutic approaches over the past several decades have focused on amyloid-beta (Aβ42) and aberrantly phosphorylated tau, which could be caused by consequences of brain insulin resistance, the broader array of pathologies including white matter atrophy with loss of myelinated fibrils and leukoaraiosis, non-Aβ42 microvascular disease, dysregulated lipid metabolism, mitochondrial dysfunction, astrocytic gliosis, neuro-inflammation, and loss of synapses vis-à-vis growth of dystrophic neurites, is not readily accounted for by Aβ42 accumulations, but could be explained by dysregulated insulin/IGF-1 signaling with attendant impairments in signal transduction and gene expression. This review covers the diverse range of brain abnormalities in AD and discusses how insulins, incretins, and insulin sensitizers could be utilized to treat at different stages of neurodegeneration.
登录
查看更多内容
DOI：
10.1016/j.jalz.2014.02.004
发表时间：
2015-01
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Blennow K;Dubois B;Fagan AM;Lewczuk P;de Leon MJ;Hampel H
通讯作者：
Hampel H
影响因子：
3.5
作者：
Aleshin, Stepan;Reiser, Georg
通讯作者：
Reiser, Georg
影响因子：
2.9
作者：
Bright, John J.;Kanakasabai, Saravanan;Chearwae, Wanida;Chakraborty, Sharmistha
通讯作者：
Chakraborty, Sharmistha
影响因子：
7.4
作者：
Aguirre GA;De Ita JR;de la Garza RG;Castilla-Cortazar I
通讯作者：
Castilla-Cortazar I
影响因子：
2.8
作者：
Bonda DJ;Wang X;Perry G;Smith MA;Zhu X
通讯作者：
Zhu X