title: MMP-mediated cleavage of beta-dystroglycan in myelin sheath is involved in autoimmune neuritis.
abstract: Alpha-/beta-dystroglycans (DG) located at the outmost layer of myelin sheath play a critical role in its formation and stability in the peripheral nerve system. The demyelination of nerve fibers is present in autoimmune neuritis, however, it is not known about the molecular mechanisms underlying this pathological process. In an animal model of experimental autoimmune neuritis, we observed that beta-DG cleavage was associated with the demyelination of peripheral nerves. The neuritis and beta-DG cleavage were accompanied by matrix metalloproteinase (MMP)-2/-9 over-expressions and attenuated by captopril, a MMP inhibitor. The blockade of MMPs also improves clinical signs. Our results reveal a crucial role of MMP-mediated beta-DG cleavage in autoimmune neuritis, such as Guillain-Barre' syndrome, and bring insights into therapeutic strategies for autoimmune diseases.
authors.affiliation: Department of Neurology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Xiu Li
authors.initials: XL
authors.lastname: Zhao
authors.forename: Guo Zhong
authors.initials: GZ
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.forename: Zhong Ling
authors.initials: ZL
authors.lastname: Zhang
authors.forename: Yan Hong
authors.initials: YH
authors.lastname: Yin
authors.forename: Yu Shuang
authors.initials: YS
authors.lastname: Tian
authors.forename: He
authors.initials: H
authors.lastname: Li
authors.forename: Hu Lun
authors.initials: HL
authors.lastname: Li
authors.forename: De Sheng
authors.initials: de S
authors.lastname: Wang
authors.forename: Di
authors.initials: D
authors.lastname: Zhong
mesh_terms: D000818:Animals; D002216:Captopril / Q000494:pharmacology; D049030:Dystroglycans / Q000378:metabolism*; D005260:Female; D020275:Guillain-Barre Syndrome / Q000378:metabolism* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology; D009444:Neuritis, Autoimmune, Experimental / Q000378:metabolism* / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D049030:Dystroglycans; D002216:Captopril; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9