Coretti Lorena, Buommino Elisabetta, Lembo Francesca
Department of Pharmacy, University of Naples Federico II, Naples, Italy.
Task Force on Microbiome Studies, University of Naples Federico II, Naples, Italy.
Front Cell Neurosci. 2024 Aug 8;18:1433747. doi: 10.3389/fncel.2024.1433747. eCollection 2024.
The Aryl hydrocarbon receptor (AHR) is a cytosolic receptor and ligand-activated transcription factor widely expressed across various cell types in the body. Its signaling is vital for host responses at barrier sites, regulating epithelial renewal, barrier integrity, and the activities of several types of immune cells. This makes AHR essential for various cellular responses during aging, especially those governing inflammation and immunity. In this review, we provided an overview of the mechanisms by which the AHR mediates inflammatory response at gut and brain level through signals from intestinal microbes. The age-related reduction of gut microbiota functions is perceived as a trigger of aberrant immune responses linking gut and brain inflammation to neurodegeneration. Thus, we explored gut microbiome impact on the nature and availability of AHR ligands and outcomes for several signaling pathways involved in neurodegenerative diseases and age-associated decline of brain functions, with an insight on Parkinson's and Alzheimer's diseases, the most common neurodegenerative diseases in the elderly. Specifically, we focused on microbial tryptophan catabolism responsible for the production of several AHR ligands. Perspectives for the development of microbiota-based interventions targeting AHR activity are presented for a healthy aging.
芳烃受体（AHR）是一种胞质受体和配体激活的转录因子，在体内多种细胞类型中广泛表达。其信号传导对于屏障部位的宿主反应至关重要，可调节上皮细胞更新、屏障完整性以及几种免疫细胞的活性。这使得AHR对于衰老过程中的各种细胞反应至关重要，尤其是那些控制炎症和免疫的反应。在本综述中，我们概述了AHR通过肠道微生物信号在肠道和大脑水平介导炎症反应的机制。肠道微生物群功能的年龄相关下降被认为是异常免疫反应的触发因素，将肠道和大脑炎症与神经退行性变联系起来。因此，我们探讨了肠道微生物群对AHR配体的性质和可用性的影响，以及对神经退行性疾病和与年龄相关的脑功能衰退所涉及的几种信号通路的影响，并深入研究了帕金森病和阿尔茨海默病这两种老年人中最常见的神经退行性疾病。具体而言，我们重点关注负责产生几种AHR配体的微生物色氨酸分解代谢。针对健康衰老，提出了基于微生物群的干预措施以靶向AHR活性的发展前景。
