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CNS Drugs
Published in: CNS Drugs 7/2013

01-07-2013 | Leading Article

Blocking LINGO-1 as a Therapy to Promote CNS Repair: From Concept to the Clinic

Authors: Sha Mi, R. Blake Pepinsky, Diego Cadavid

Published in: CNS Drugs | Issue 7/2013

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Abstract

LINGO-1 is a leucine-rich repeat and Ig domain-containing, Nogo receptor interacting protein, selectively expressed in the CNS on both oligodendrocytes and neurons. Its expression is developmentally regulated, and is upregulated in CNS diseases and injury. In animal models, LINGO-1 expression is upregulated in rat spinal cord injury, experimental autoimmune encephalomyelitis, 6-hydroxydopamine neurotoxic lesions and glaucoma models. In humans, LINGO-1 expression is increased in oligodendrocyte progenitor cells from demyelinated white matter of multiple sclerosis post-mortem samples, and in dopaminergic neurons from Parkinson’s disease brains. LINGO-1 negatively regulates oligodendrocyte differentiation and myelination, neuronal survival and axonal regeneration by activating ras homolog gene family member A (RhoA) and inhibiting protein kinase B (Akt) phosphorylation signalling pathways. Across diverse animal CNS disease models, targeted LINGO-1 inhibition promotes neuron and oligodendrocyte survival, axon regeneration, oligodendrocyte differentiation, remyelination and functional recovery. The targeted inhibition of LINGO-1 function presents a novel therapeutic approach for the treatment of CNS diseases.

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Metadata
Title
Blocking LINGO-1 as a Therapy to Promote CNS Repair: From Concept to the Clinic
Authors
Sha Mi
R. Blake Pepinsky
Diego Cadavid
Publication date
01-07-2013
Publisher
Springer International Publishing
Published in
CNS Drugs / Issue 7/2013
Print ISSN: 1172-7047
Electronic ISSN: 1179-1934
DOI
https://doi.org/10.1007/s40263-013-0068-8

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