Cerebral Fructose Metabolism as a Potential Mechanism Driving Alzheimer's Disease.
Cerebral Fructose Metabolism as a Potential Mechanism Driving Alzheimer's Disease.
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DOI：
10.3389/fnagi.2020.560865
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发表时间：
2020
影响因子：
4.8
通讯作者：
Lanaspa MA
中科院分区：
文献类型：
--
作者：
Johnson RJ;Gomez-Pinilla F;Nagel M;Nakagawa T;Rodriguez-Iturbe B;Sanchez-Lozada LG;Tolan DR;Lanaspa MA
阿尔茨海默病中认知功能的丧失在病理上与神经元缠结、淀粉样蛋白沉积和神经元通信的丧失相关。脑胰岛素抵抗和线粒体功能障碍已成为支持我们的假设，脑果糖代谢是阿尔茨海默病的关键起始途径的发病机制的重要贡献者。果糖在营养素中是独特的，因为它通过降低细胞中与腺苷酸降解为尿酸相关的能量来激活生存途径以保护动物免于饥饿。果糖代谢的能量下降刺激觅食和食物摄入，同时通过降低线粒体功能、刺激糖酵解和诱导胰岛素抵抗来减少能量和氧气需求。当果糖代谢系统性过度激活时，例如过量摄入果糖，这可能导致肥胖和糖尿病。在此，我们提出的证据表明，阿尔茨海默病可能是由大脑果糖代谢的过度激活，其中果糖的来源主要是从大脑中的内源性生产驱动。因此，线粒体能量产生的减少受到神经元糖酵解不充分的阻碍，导致神经元保持功能和活力所需的脑能量水平逐渐丧失。从本质上讲，我们认为阿尔茨海默病是一种现代疾病，由饮食生活方式的变化驱动，其中果糖可以破坏大脑代谢和神经元功能。抑制脑内果糖代谢可能为该病的防治提供新的途径。
The loss of cognitive function in Alzheimer’s disease is pathologically linked with neurofibrillary tangles, amyloid deposition, and loss of neuronal communication. Cerebral insulin resistance and mitochondrial dysfunction have emerged as important contributors to pathogenesis supporting our hypothesis that cerebral fructose metabolism is a key initiating pathway for Alzheimer’s disease. Fructose is unique among nutrients because it activates a survival pathway to protect animals from starvation by lowering energy in cells in association with adenosine monophosphate degradation to uric acid. The fall in energy from fructose metabolism stimulates foraging and food intake while reducing energy and oxygen needs by decreasing mitochondrial function, stimulating glycolysis, and inducing insulin resistance. When fructose metabolism is overactivated systemically, such as from excessive fructose intake, this can lead to obesity and diabetes. Herein, we present evidence that Alzheimer’s disease may be driven by overactivation of cerebral fructose metabolism, in which the source of fructose is largely from endogenous production in the brain. Thus, the reduction in mitochondrial energy production is hampered by neuronal glycolysis that is inadequate, resulting in progressive loss of cerebral energy levels required for neurons to remain functional and viable. In essence, we propose that Alzheimer’s disease is a modern disease driven by changes in dietary lifestyle in which fructose can disrupt cerebral metabolism and neuronal function. Inhibition of intracerebral fructose metabolism could provide a novel way to prevent and treat this disease.
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影响因子：
6.7
作者：
Gomez-Pinilla F;Yang X
通讯作者：
Yang X
DOI：
10.1038/nrneurol.2017.185
发表时间：
2018-03
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
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通讯作者：
Nathan DM
影响因子：
3.7
作者：
Cheng XJ;Gao Y;Zhao YW;Cheng XD
通讯作者：
Cheng XD
影响因子：
5.5
作者：
Agrawal, Rahul;Gomez-Pinilla, Fernando
通讯作者：
Gomez-Pinilla, Fernando
影响因子：
3.3
作者：
al-Dahhak, Roula;Khoury, Rita;Grossberg, George T.
通讯作者：
Grossberg, George T.