神经炎症
神经退行性变
肠道菌群
认知功能衰退
血脑屏障
药理学
代谢物
阿尔茨海默病
肠-脑轴
医学
神经科学
化学
中枢神经系统
内科学
疾病
生物
免疫学
痴呆
作者
Xiao Guo,Chen Li,Jia Zhang,Maozhong Sun,Jun Xu,Chuanlai Xu,Hua Kuang,Liguang Xu
出处
期刊:Nature Aging
日期:2023-11-09
卷期号:3 (11): 1415-1429
被引量:16
标识
DOI:10.1038/s43587-023-00516-9
摘要
Alzheimer's disease (AD) is characterized by amyloid-β accumulation in the brain and hyperphosphorylated tau aggregation, as well as neuroinflammation. The gut–brain axis has emerged as a therapeutic target in neurodegenerative diseases by modulating metabolic activity, neuroimmune functions and sensory neuronal signaling. Here we investigate interactions between orally ingested chiral Au nanoparticles and the gut microbiota in AD mice. Oral administration of chiral Au nanoparticles restored cognitive abilities and ameliorated amyloid-β and hyperphosphorylated tau pathologies in AD mice via alterations in the gut microbiome composition and an increase in the gut metabolite, indole-3-acetic acid, which was lower in serum and cerebrospinal fluid of patients with AD compared with age-matched controls. Oral administration of indole-3-acetic acid was able to penetrate the blood–brain barrier and alleviated cognitive decline and pathology including neuroinflammation in AD mice. These findings provide a promising therapeutic target for the amelioration of neuroinflammation and treatment of neurodegenerative diseases. Guo et al. demonstrate that oral administration of chiral nanoparticles ameliorates Alzheimer's disease-associated pathology and cognitive decline in mice via an increase in the gut metabolite, indole-3-acetic acid, potentially a therapeutic target.
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