LINGO-1 antagonists as therapy for multiple sclerosis: in vitro and in vivo evidence

Expert Opin Biol Ther. 2008 Oct;8(10):1561-70. doi: 10.1517/14712598.8.10.1561.

Abstract

Background: Multiple sclerosis (MS) is an inflammatory disease of the CNS that causes progressive neurological disability in most patients. Certain alleles of immunity-associated genes increase risk of MS, confirming a role for autoimmune mechanisms in pathogenesis. Activated mononuclear cells infiltrate the CNS and trigger an inflammatory cascade, resulting in demyelination and axonal injury. Non-inflammatory mechanisms also appear to be involved in axonal degeneration but are not fully elucidated. Current therapies are anti-inflammatory, and no available therapy is known to promote myelin repair or maintenance. Leucine-rich repeats and Ig domain-containing, neurite outgrowth inhibitor (Nogo) receptor-interacting protein-1 (LINGO-1) is a potent negative regulator of axonal myelination.

Objective/methods: This article provides an overview of the available data on the effects of LINGO-1 antagonists on oligodendrocyte differentiation and remyelination.

Results/conclusion: LINGO-1 is a potential target for neuroprotective therapy in that antagonists may promote remyelination in diseases such as MS.

Publication types

  • Review

MeSH terms

  • Cell Differentiation
  • Humans
  • Membrane Proteins / antagonists & inhibitors*
  • Multiple Sclerosis / drug therapy*
  • Nerve Tissue Proteins / antagonists & inhibitors*
  • Oligodendroglia / cytology
  • Oligodendroglia / drug effects

Substances

  • LINGO1 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins