PRDX6 controls multiple sclerosis by suppressing inflammation and blood brain barrier disruption.
Multiple sclerosis (MS) is a complex disease with an unknown etiology and has no effective medications despite extensive research. Antioxidants suppress oxidative damages which are implicated in the pathogenesis of MS. In this study, we showed that the expression of an antioxidant protein peroxiredoxin 6 (PRDX6) is markedly increased in spinal cord of mice with experimental autoimmune encephalomyelitis (EAE) compared to other PRDXs. PRDX6 transgenic (Tg) mice displayed a significant decrease in clinical severity and attenuated demyelination in EAE compared to wide type mice. The increased PRDX6 expression in astrocytes of EAE mice and MS patients reduced MMP9 expression, fibrinogen leakage, chemokines, and free radical stress, leading to reduction in blood-brain-barrier (BBB) disruption, peripheral immune cell infiltration, and neuroinflammation. Together, these findings suggest that PRDX6 expression may represent a therapeutic way to restrict inflammation in the central nervous system and potentiate oligodendrocyte survival, and suggest a new molecule for neuroprotective therapies in MS.
Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Dongdaemun-gu, Republic of Korea.
Hyung-Mun
HM
Yun
Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Dongdaemun-gu, Republic of Korea.
Kyung-Ran
KR
Park
Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University, Dongdaemun-gu, Republic of Korea.
Eun-Cheol
EC
Kim
College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Jin Tae
JT
Hong
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D020869:Gene Expression Profiling; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000276:immunology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology; D054465:Peroxiredoxin VI / Q000276:immunology / Q000502:physiology*; D020543:Proteome; D017382:Reactive Oxygen Species / Q000378:metabolism
D020543:Proteome; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D054465:Peroxiredoxin VI; C515983:Prdx6 protein, mouse
EAE; PRDX6; Pathology Section; astrocytes; demyelination; inflammation; multiple sclerosis