期刊
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
卷 9, 期 7, 页码 -出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/cshperspect.a034223
关键词
-
资金
- National Multiple Sclerosis Society
The alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) is central to the anti-inflammatory function of the vagus nerve in a physiological mechanism termed the inflammatory reflex. Studies on the inflammatory reflex have been instrumental for the current development of the field of bioelectronic medicine. An independent investigation of the biological role of alpha B-crystallin (HspB5), the most abundant gene transcript present in active multiple sclerosis lesions in human brains, also led to alpha 7nAChR. Induction of experimental autoimmune encephalomyelitis (EAE) in HspB5(-/-) mice results in greater paralytic signs, increased levels of proinflammatory cytokines, and T-lymphocyte activation relative to wild-type animals. Administration of HspB5 was therapeutic in animal models of multiple sclerosis, retinal and cardiac ischemia, and stroke. Structure-activity studies established that residues 73-92 were as potent as the parent protein, but only when it formed amyloid fibrils. Amyloid fibrils and small heat shock proteins (sHsps) selectively bound alpha 7nAChR on peritoneal macrophages (M Phi s) and B lymphocytes, converting the M Phi s to an immune suppressive phenotype and mobilizing the migration of both cell types from the peritoneum to secondary lymph organs. Here, we review multiple aspects of this work, which may be of interest for developing future therapeutic approaches for multiple sclerosis and other disorders.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据