LINGO-1 antagonists as therapy for multiple sclerosis: in vitro and in vivo evidence.
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
This article provides an overview of the available data on the effects of LINGO-1 antagonists on oligodendrocyte differentiation and remyelination.


CONCLUSIONS
LINGO-1 is a potential target for neuroprotective therapy in that antagonists may promote remyelination in diseases such as MS.
Rudick
Richard A
RA
Mellen Center for Multiple Sclerosis Treatment and Research, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. rudickr@ccf.org
Mi
Sha
S
Sandrock
Alfred W
AW
D002454:Cell Differentiation; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D009103:Multiple Sclerosis / Q000188:drug therapy*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects
C482293:LINGO1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins