The interplay among oxidative stress, brain insulin resistance and AMPK dysfunction contribute to neurodegeneration in type 2 diabetes and Alzheimer disease.
The interplay among oxidative stress, brain insulin resistance and AMPK dysfunction contribute to neurodegeneration in type 2 diabetes and Alzheimer disease.
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DOI：
10.1016/j.freeradbiomed.2021.09.006
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发表时间：
2021-11-20
影响因子：
7.4
通讯作者：
Butterfield DA
中科院分区：
文献类型：
--
作者：
Barone E;Di Domenico F;Perluigi M;Butterfield DA
阿尔茨海默病（AD）是老年人中最常见的痴呆形式，其次是血管性痴呆。除了临床诊断的痴呆症外，还报告了糖尿病患者的认知功能障碍。最近的研究现在开始认识到2型糖尿病（T2DM），其特征是慢性高血糖和胰岛素抵抗，是AD和其他认知障碍的危险因素。虽然对胰岛素作用的研究传统上仍停留在外周组织领域，但在最近的临床和临床前研究中越来越多地报道了中枢神经系统中胰岛素抵抗对认知功能障碍的有害影响。大脑功能需要持续的葡萄糖和氧气供应以及对代谢过程的严格调节。这种代谢调节的丧失被认为是与神经变性相关的记忆功能障碍的一个因素。在上述情况下，这篇综述将集中在氧化应激（OS），胰岛素抵抗和AMPK功能障碍之间的相互作用，在大脑中突出这些神经毒性事件如何有助于神经变性。我们提供了OS对调节胰岛素信号的蛋白质的有害影响以及这些改变如何通过AMPK失调影响细胞代谢功能障碍的概述。我们断言，这些过程与AD的分子通路密切相关。
Alzheimer’s disease (AD) is the most common form of dementia in the elderly followed by vascular dementia. In addition to clinically diagnosed dementia, cognitive dysfunction has been reported in diabetic patients. Recent studies are now beginning to recognize type 2 diabetes mellitus (T2DM), characterized by chronic hyperglycemia and insulin resistance, as a risk factor for AD and other cognitive disorders. While studies on insulin action have remained traditionally in the domain of peripheral tissues, the detrimental effects of insulin resistance in the central nervous system on cognitive dysfunction are increasingly being reported in recent clinical and preclinical studies. Brain functions require continuous supply of glucose and oxygen and a tight regulation of metabolic processes. Loss of this metabolic regulation has been proposed to be a contributor to memory dysfunction associated with neurodegeneration. Within the above scenario, this review will focus on the interplay among oxidative stress (OS), insulin resistance and AMPK dysfunctions in the brain by highlighting how these neurotoxic events contribute to neurodegeneration. We provide an overview on the detrimental effects of OS on proteins regulating insulin signaling and how these alterations impact cell metabolic dysfunctions through AMPK dysregulation. Such processes, we assert, are critically involved in the molecular pathways that underlie AD.
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DOI：
10.1038/nrneurol.2017.185
发表时间：
2018-03
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
Arnold SE;Arvanitakis Z;Macauley-Rambach SL;Koenig AM;Wang HY;Ahima RS;Craft S;Gandy S;Buettner C;Stoeckel LE;Holtzman DM;Nathan DM
通讯作者：
Nathan DM
胰岛素信号障碍，脂联素和血脂异常在小鼠外周和中枢神经病中的作用。
影响因子：
4.3
作者：
Anderson NJ;King MR;Delbruck L;Jolivalt CG
通讯作者：
Jolivalt CG
影响因子：
6.1
作者：
Arnold SE;Lucki I;Brookshire BR;Carlson GC;Browne CA;Kazi H;Bang S;Choi BR;Chen Y;McMullen MF;Kim SF
通讯作者：
Kim SF
影响因子：
3.7
作者：
Backeström A;Papadopoulos K;Eriksson S;Olsson T;Andersson M;Blennow K;Zetterberg H;Nyberg L;Rolandsson O
通讯作者：
Rolandsson O
影响因子：
4.7
作者：
Barone, Eugenio;Mancuso, Cesare;Butterfield, D. Allan
通讯作者：
Butterfield, D. Allan