近期,，國際著名學術(shù)期刊《自然醫(yī)學》（Nature Medicine）最新一期發(fā)表了健康所錢友存研究員對于學術(shù)論文“Peli1 promotes microglia-mediated CNS inflammation by regulating Traf3 degradation”的題為“Peli1 sets the CNS on fire”的精彩點評。
多發(fā)性硬化（Multiple Sclerosis,，MS）是一種中樞神經(jīng)系統(tǒng)炎癥損傷性自身免疫病,，其發(fā)病機制尚不清楚。小神經(jīng)膠質(zhì)細胞（microglia）在MS炎癥性病理中發(fā)揮著關(guān)鍵性作用,。錢友存研究員綜合分析了相關(guān)研究領(lǐng)域進展,，強調(diào)了該研究成果的重要意義在于通過小鼠疾病模型研究發(fā)現(xiàn)調(diào)控小神經(jīng)膠質(zhì)細胞激活的關(guān)鍵調(diào)節(jié)因子Peli1，并闡明其在調(diào)控MS病理中的功能與作用機制,，為MS及相關(guān)疾病的治療提供了重要理論基礎(chǔ)與潛在新靶點,，并討論了尚待進一步解決的關(guān)鍵科學問題及針對性研發(fā)治療新策略的措施。(生物谷Bioon.com)
生物谷推薦英文摘要1：
Nature Medicine doi:10.1038/nm.3176
Peli1 sets the CNS on fire
It has long been unknown how activation of resident macrophages in the brain, or microglia, is regulated during the inflammatory pathogenesis of multiple sclerosis. Work in a mouse model of human multiple sclerosis identifies the E3 ubiquitin ligase Peli1 as a new crucial regulator of microglia activation
生物谷推薦英文摘要2：
Nature Medicine doi:10.1038/nm.3111
Peli1 promotes microglia-mediated CNS inflammation by regulating Traf3 degradation
Microglia are crucial for the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Here we show that the E3 ubiquitin ligase Peli1 is abundantly expressed in microglia and promotes microglial activation during the course of EAE induction. Peli1 mediates the induction of chemokines and proinflammatory cytokines in microglia and thereby promotes recruitment of T cells into the central nervous system. The severity of EAE is reduced in Peli1-deficient mice despite their competent induction of inflammatory T cells in the peripheral lymphoid organs. Notably, Peli1 regulates Toll-like receptor (TLR) pathway signaling by promoting degradation of TNF receptor–associated factor 3 (Traf3), a potent inhibitor of mitogen-activated protein kinase (MAPK) activation and gene induction. Ablation of Traf3 restores microglial activation and CNS inflammation after the induction of EAE in Peli1-deficient mice. These findings establish Peli1 as a microglia-specific mediator of autoimmune neuroinflammation and suggest a previously unknown signaling mechanism of Peli1 function.
