Modulating proteoglycan receptor PTPσ using intracellular sigma peptide improves remyelination and functional recovery in mice with demyelinated optic chiasm.

Abstract

Multiple sclerosis (MS) is an autoimmune disease characterized by myelin and axonal damage in the central nervous system (CNS). Glial scar which is a hallmark of MS contains repair inhibitory molecules including chondroitin sulfate proteoglycans (CSPGs). CSPGs inhibit repair of damaged area through various receptors including protein tyrosine phosphatase sigma (PTPσ). In the current study we use intracellular sigma peptide (ISP), an inhibitor of PTPσ signaling, in LPC-induced focal demyelination of mouse optic chiasm. ISP treatment resulted in decreased demyelination, reduced astrogliosis, and increased newly generated oligodendrocytes which subsequently led to enhanced remyelination. Analyzing of electrophysiological (as performed by visual evoked potential recording) and behavioral (performed by visual cliff test) outcomes showed that ISP-treatment improved the integrity of optic pathway as well as the visual acuity. When ISP was administrated only during the repair phase, histological, electrophysiological and behavioral studies showed its regenerative effect. Our results demonstrated the possibility of using ISP as a new strategy to inhibit PTPσ for myelin protection, myelin repair in demyelinated axons, and functional neural pathway conductivity restoration in patients suffering from MS.

• Authors: Parvin Niknam, Mohammad Reza Raoufy, Yaghoub Fathollahi, Mohammad Javan
• Journal: Molecular and cellular neurosciences (Mol Cell Neurosci) Vol. 99 Pg. 103391 (09 2019) ISSN: 1095-9327 [Electronic] United States
• PMID: 31276750 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Peptides
• Receptor-Like Protein Tyrosine Phosphatases, Class 2

Topics

• Animals
• Evoked Potentials, Visual
• Male
• Mice
• Mice, Inbred C57BL
• Multiple Sclerosis (drug therapy)
• Myelin Sheath (metabolism)
• Oligodendroglia (drug effects, metabolism)
• Optic Chiasm (drug effects, metabolism, physiology)
• Peptides (pharmacology, therapeutic use)
• Protein Binding
• Receptor-Like Protein Tyrosine Phosphatases, Class 2 (antagonists & inhibitors, chemistry, metabolism)