Lushuang Xie, Qiaofeng Wu, Kelin Li, Mohammed A S Khan, Andrew Zhang, Bharati Sinha, Sihui Li, Sulie L Chang, David L Brody, Mark W Grinstaff, Shuanhu Zhou, Gil Alterovitz, Pinghua Liu, Xin Wang
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引用次数: 0
Abstract
Alzheimer's disease (AD) is an age-dependent neurodegenerative disease characterized by extracellular Amyloid Aβ peptide (Aβ) deposition and intracellular Tau protein aggregation. Glia, especially microglia and astrocytes are core participants during the progression of AD and these cells are the mediators of Aβ clearance and degradation. The microbiota-gut-brain axis (MGBA) is a complex interactive network between the gut and brain involved in neurodegeneration. MGBA affects the function of glia in the central nervous system (CNS), and microbial metabolites regulate the communication between astrocytes and microglia; however, whether such communication is part of AD pathophysiology remains unknown. One of the potential links in bilateral gut-brain communication is tryptophan (Trp) metabolism. The microbiota-originated Trp and its metabolites enter the CNS to control microglial activation, and the activated microglia subsequently affect astrocyte functions. The present review highlights the role of MGBA in AD pathology, especially the roles of Trp per se and its metabolism as a part of the gut microbiota and brain communications. We (i) discuss the roles of Trp derivatives in microglia-astrocyte crosstalk from a bioinformatics perspective, (ii) describe the role of glia polarization in the microglia-astrocyte crosstalk and AD pathology, and (iii) summarize the potential of Trp metabolism as a therapeutic target. Finally, we review the role of Trp in AD from the perspective of the gut-brain axis and microglia, as well as astrocyte crosstalk, to inspire the discovery of novel AD therapeutics.
阿尔茨海默病(AD)是一种依赖年龄的神经退行性疾病,以细胞外淀粉样 Aβ 肽(Aβ)沉积和细胞内 Tau 蛋白聚集为特征。神经胶质细胞,尤其是小胶质细胞和星形胶质细胞,是 AD 进展过程中的核心参与者,这些细胞是 Aβ 清除和降解的媒介。微生物群-肠-脑轴(MGBA)是肠道和大脑之间的一个复杂的互动网络,参与神经退行性病变。MGBA影响中枢神经系统(CNS)神经胶质细胞的功能,微生物代谢产物调节星形胶质细胞和小胶质细胞之间的交流;然而,这种交流是否是AD病理生理学的一部分仍是未知数。色氨酸(Trp)代谢是肠道-大脑双边交流的潜在环节之一。微生物群产生的 Trp 及其代谢产物进入中枢神经系统,控制小胶质细胞的活化,活化的小胶质细胞随后影响星形胶质细胞的功能。本综述强调了MGBA在AD病理学中的作用,尤其是Trp本身及其代谢作为肠道微生物群和大脑交流的一部分所发挥的作用。我们(i)从生物信息学的角度讨论了Trp衍生物在小胶质细胞-星形胶质细胞串扰中的作用,(ii)描述了胶质细胞极化在小胶质细胞-星形胶质细胞串扰和AD病理学中的作用,(iii)总结了Trp代谢作为治疗靶点的潜力。最后,我们从肠道-大脑轴和小胶质细胞以及星形胶质细胞串扰的角度回顾了 Trp 在 AD 中的作用,以启发新型 AD 治疗方法的发现。
期刊介绍:
Aging & Disease (A&D) is an open-access online journal dedicated to publishing groundbreaking research on the biology of aging, the pathophysiology of age-related diseases, and innovative therapies for conditions affecting the elderly. The scope encompasses various diseases such as Stroke, Alzheimer's disease, Parkinson’s disease, Epilepsy, Dementia, Depression, Cardiovascular Disease, Cancer, Arthritis, Cataract, Osteoporosis, Diabetes, and Hypertension. The journal welcomes studies involving animal models as well as human tissues or cells.