RRC ID 51542
著者 E L, Zhou T, Koh S, Chuang M, Sharma R, Pujol N, Chisholm AD, Eroglu C, Matsunami H, Yan D.
タイトル An Antimicrobial Peptide and Its Neuronal Receptor Regulate Dendrite Degeneration in Aging and Infection.
ジャーナル Neuron
Abstract Infections have been identified as possible risk factors for aging-related neurodegenerative diseases, but it remains unclear whether infection-related immune molecules have a causative role in neurodegeneration during aging. Here, we reveal an unexpected role of an epidermally expressed antimicrobial peptide, NLP-29 (neuropeptide-like protein 29), in triggering aging-associated dendrite degeneration in C. elegans. The age-dependent increase of nlp-29 expression is regulated by the epidermal tir-1/SARM-pmk-1/p38 MAPK innate immunity pathway. We further identify an orphan G protein-coupled receptor NPR-12 (neuropeptide receptor 12) acting in neurons as a receptor for NLP-29 and demonstrate that the autophagic machinery is involved cell autonomously downstream of NPR-12 to transduce degeneration signals. Finally, we show that fungal infections cause dendrite degeneration using a similar mechanism as in aging, through NLP-29, NPR-12, and autophagy. Our findings reveal an important causative role of antimicrobial peptides, their neuronal receptors, and the autophagy pathway in aging- and infection-associated dendrite degeneration.
巻・号 97(1)
ページ 125-138.e5
公開日 2018-1-3
DOI 10.1016/j.neuron.2017.12.001
PII S0896-6273(17)31124-8
PMID 29301098
PMC PMC5757245
MeSH Aging / immunology Aging / metabolism* Aging / pathology Animals Antimicrobial Cationic Peptides / metabolism* Autophagy / physiology Caenorhabditis elegans Dendrites / metabolism Dendrites / pathology* Mycoses / immunology Mycoses / pathology Nerve Degeneration / immunology Nerve Degeneration / metabolism* Rats Receptors, G-Protein-Coupled / metabolism
IF 14.415
引用数 9
リソース情報
線虫 tm1498 tm1931