Modulation of proteoglycan receptor PTPσ enhances MMP-2 activity to promote recovery from multiple sclerosis

Fucheng Luo, Amanda Phuong Tran, Li Xin, Chandrika Sanapala, Bradley T. Lang, Jerry Silver () and Yan Yang ()
Additional contact information
Fucheng Luo: Case Western Reserve University School of Medicine
Amanda Phuong Tran: Case Western Reserve University School of Medicine
Li Xin: Case Western Reserve University School of Medicine
Chandrika Sanapala: Case Western Reserve University School of Medicine
Bradley T. Lang: BioEnterprise
Jerry Silver: Case Western Reserve University School of Medicine
Yan Yang: Case Western Reserve University School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract Multiple Sclerosis (MS) is characterized by focal CNS inflammation leading to the death of oligodendrocytes (OLs) with subsequent demyelination, neuronal degeneration, and severe functional deficits. Inhibitory chondroitin sulfate proteoglycans (CSPGs) are increased in the extracellular matrix in the vicinity of MS lesions and are thought to play a critical role in myelin regeneration failure. We here show that CSPGs curtail remyelination through binding with their cognate receptor, protein tyrosine phosphatase σ (PTPσ) on oligodendrocyte progenitor cells (OPCs). We report that inhibition of CSPG/PTPσ signaling by systemically deliverable Intracellular Sigma Peptide (ISP), promotes OPC migration, maturation, remyelination, and functional recovery in animal models of MS. Furthermore, we report a downstream molecular target of PTPσ modulation in OPCs involving upregulation of the protease MMP-2 that allows OPCs to enzymatically digest their way through CSPGs. In total, we demonstrate a critical role of PTPσ/CSPG interactions in OPC remyelination in MS.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-06505-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06505-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-06505-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().