Energy Crisis Links to Autophagy and Ferroptosis in Alzheimer's Disease: Current Evidence and Future Avenues.
Energy Crisis Links to Autophagy and Ferroptosis in Alzheimer's Disease: Current Evidence and Future Avenues.
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DOI：
10.2174/1570159x20666220817140737
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发表时间：
2023
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
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作者：
阿尔茨海默病（AD）是全世界最常见的神经退行性疾病之一。发病的隐匿性和病因学的不确定性在很大程度上阻碍了 AD 治疗策略的制定。既往研究表明，AD患者大脑中能量代谢紊乱的出现远早于AD典型病理特征，提示能量危机与AD发病之间存在密切联系。已知大脑中的能量危机是由葡萄糖摄取和利用减少引起的，这可能归因于脑葡萄糖转运蛋白（GLUT）表达减少、胰岛素抵抗、线粒体功能障碍和乳酸代谢障碍。值得注意的是，过氧化物酶体增殖物激活受体（PPAR）、转录因子EB（TFEB）和AMP激活蛋白激酶（AMPK）等能量传感器被证明是自噬的关键调节因子，在调节β-淀粉样蛋白（Aβ）代谢、tau磷酸化、神经炎症、铁动力学以及铁死亡中发挥重要作用。在这项研究中，我们总结了目前关于 AD 能量代谢异常分子机制的知识，并讨论了能量危机、自噬和铁死亡之间存在的相互作用。此外，我们强调了自噬可能作为 AD 进展中能量危机和铁死亡之间桥梁的潜在网络。更深入地了解能量代谢障碍与 AD 之间的关系可能会为制定治疗 AD 的策略提供新的见解；与此同时，AD发展中的能源危机应引起更多关注。
Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases worldwide. The occult nature of the onset and the uncertainty of the etiology largely impede the development of therapeutic strategies for AD. Previous studies revealed that the disorder of energy metabolism in the brains of AD patients appears far earlier than the typical pathological features of AD, suggesting a tight association between energy crisis and the onset of AD. Energy crisis in the brain is known to be induced by the reductions in glucose uptake and utilization, which may be ascribed to the diminished expressions of cerebral glucose transporters (GLUTs), insulin resistance, mitochondrial dysfunctions, and lactate dysmetabolism. Notably, the energy sensors such as peroxisome proliferators-activated receptor (PPAR), transcription factor EB (TFEB), and AMP-activated protein kinase (AMPK) were shown to be the critical regulators of autophagy, which play important roles in regulating beta-amyloid (Aβ) metabolism, tau phosphorylation, neuroinflammation, iron dynamics, as well as ferroptosis. In this study, we summarized the current knowledge on the molecular mechanisms involved in the energy dysmetabolism of AD and discussed the interplays existing between energy crisis, autophagy, and ferroptosis. In addition, we highlighted the potential network in which autophagy may serve as a bridge between energy crisis and ferroptosis in the progression of AD. A deeper understanding of the relationship between energy dysmetabolism and AD may provide new insight into developing strategies for treating AD; meanwhile, the energy crisis in the progression of AD should gain more attention.
影响因子：
6.8
作者：
Das, Abhijit;Bhattacharya, Barshana;Roy, Souvik
通讯作者：
Roy, Souvik