Brain metabolic stress and neuroinflammation at the basis of cognitive impairment in Alzheimer's disease.
Brain metabolic stress and neuroinflammation at the basis of cognitive impairment in Alzheimer's disease.
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DOI：
10.3389/fnagi.2015.00094
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发表时间：
2015
影响因子：
4.8
通讯作者：
Lourenco MV
中科院分区：
文献类型：
--
作者：
De Felice FG;Lourenco MV
已知脑代谢功能障碍会影响包括阿尔茨海默病（AD）在内的几种神经系统疾病的脑活动。事实上，神经元代谢的失调已被假定为在导致AD中观察到的临床结果中发挥关键作用。除了AD患者中葡萄糖利用的缺陷之外，最近的证据表明神经炎症和内质网（ER）应激是AD和其他神经系统疾病中发展的新型脑代谢应激的组成部分。在这里，我们回顾研究结果支持这种新的范式，并进一步讨论这些机制似乎参与突触和认知障碍，密切相关的AD。这些有害的过程类似于在外周组织中起作用的途径，导致胰岛素抵抗和葡萄糖耐受不良，在一个有趣的分子连接中将AD与糖尿病联系起来。发现导致神经元代谢应激的详细机制可能是理解AD中认知障碍如何发展的关键一步，从而为有效的疾病预防和治疗靶向提供新的途径。
Brain metabolic dysfunction is known to influence brain activity in several neurological disorders, including Alzheimer’s disease (AD). In fact, deregulation of neuronal metabolism has been postulated to play a key role leading to the clinical outcomes observed in AD. Besides deficits in glucose utilization in AD patients, recent evidence has implicated neuroinflammation and endoplasmic reticulum (ER) stress as components of a novel form of brain metabolic stress that develop in AD and other neurological disorders. Here we review findings supporting this novel paradigm and further discuss how these mechanisms seem to participate in synapse and cognitive impairments that are germane to AD. These deleterious processes resemble pathways that act in peripheral tissues leading to insulin resistance and glucose intolerance, in an intriguing molecular connection linking AD to diabetes. The discovery of detailed mechanisms leading to neuronal metabolic stress may be a key step that will allow the understanding how cognitive impairment develops in AD, thereby offering new avenues for effective disease prevention and therapeutic targeting.