Advertisement
ResearchIn-Press PreviewNeuroscience Open Access | 10.1172/JCI176910
1Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
2Division of Medical Sciences, University of Victoria, Victoria, Canada
3Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Find articles by Ghorbani, S. in: JCI | PubMed | Google Scholar
1Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
2Division of Medical Sciences, University of Victoria, Victoria, Canada
3Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Find articles by Li, C. in: JCI | PubMed | Google Scholar
1Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
2Division of Medical Sciences, University of Victoria, Victoria, Canada
3Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Find articles by Lozinski, B. in: JCI | PubMed | Google Scholar
1Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
2Division of Medical Sciences, University of Victoria, Victoria, Canada
3Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Find articles by Moezzi, D. in: JCI | PubMed | Google Scholar
1Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
2Division of Medical Sciences, University of Victoria, Victoria, Canada
3Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Find articles by D'Mello, C. in: JCI | PubMed | Google Scholar
1Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
2Division of Medical Sciences, University of Victoria, Victoria, Canada
3Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Find articles by Dong, Y. in: JCI | PubMed | Google Scholar
1Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
2Division of Medical Sciences, University of Victoria, Victoria, Canada
3Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Find articles by Visser, F. in: JCI | PubMed | Google Scholar
1Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
2Division of Medical Sciences, University of Victoria, Victoria, Canada
3Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Find articles by Li, H. in: JCI | PubMed | Google Scholar
1Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
2Division of Medical Sciences, University of Victoria, Victoria, Canada
3Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Find articles by Silva, C. in: JCI | PubMed | Google Scholar
1Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
2Division of Medical Sciences, University of Victoria, Victoria, Canada
3Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Find articles by Khakpour, M. in: JCI | PubMed | Google Scholar
1Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
2Division of Medical Sciences, University of Victoria, Victoria, Canada
3Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Find articles by Murray, C. in: JCI | PubMed | Google Scholar
1Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
2Division of Medical Sciences, University of Victoria, Victoria, Canada
3Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Find articles by Tremblay, M. in: JCI | PubMed | Google Scholar
1Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
2Division of Medical Sciences, University of Victoria, Victoria, Canada
3Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Find articles by Xue, M. in: JCI | PubMed | Google Scholar
1Hotchkiss Brain Institute and Department of Clinical Neurosciences, University of Calgary, Calgary, Canada
2Division of Medical Sciences, University of Victoria, Victoria, Canada
3Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
Find articles by Yong, V. in: JCI | PubMed | Google Scholar |
Published May 14, 2024 - More info
Impairment of oligodendrocytes and myelin contributes to neurological disorders including multiple sclerosis (MS), stroke and Alzheimer's disease. Regeneration of myelin (remyelination) decreases the vulnerability of demyelinated axons, but this repair process commonly fails with disease progression. A contributor to inefficient remyelination is the altered extracellular matrix (ECM) in lesions that remains to be better defined. We have identified fibulin-2 (FBLN2) as a highly upregulated ECM component in lesions of MS and stroke, and in proteome databases of Alzheimer’s disease and traumatic brain injury. Focusing on MS, the inhibitory role of FBLN2 was suggested in the experimental autoimmune encephalomyelitis (EAE) model in which genetic FBLN2 deficiency improved behavioral recovery by promoting the maturation of oligodendrocytes and enhancing remyelination. Mechanistically, when oligodendrocyte progenitors were cultured in differentiation media, FBLN2 impeded their maturation into oligodendrocytes by engaging the Notch pathway, leading to cell death. Adeno-associated virus-deletion of FBLN2 in astrocytes improved oligodendrocyte numbers and functional recovery in EAE and generated new myelin profiles after lysolecithin-induced demyelination. Collectively, our findings implicate FBLN2 as a hitherto unrecognized injury-elevated ECM, and a therapeutic target, that impairs oligodendrocyte maturation and myelin repair.