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

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 upr...

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Bibliographic Details
Published in:	CNS drugs Vol. 27; no. 7; pp. 493 - 503
Main Authors:	Mi, Sha, Blake Pepinsky, R., Cadavid, Diego
Format:	Journal Article
Language:	English
Published:	Cham Springer International Publishing 01.07.2013 Springer Nature B.V
Subjects:	Aging - metabolism Aging - pathology Animals Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal - therapeutic use Brain Cell Survival - drug effects Central Nervous System Diseases - drug therapy Central Nervous System Diseases - metabolism Central Nervous System Diseases - pathology Clinical Trials as Topic Disease Glaucoma Humans Leading Article Medical imaging Medicine Medicine & Public Health Membrane Proteins - antagonists & inhibitors Membrane Proteins - biosynthesis Nerve Tissue Proteins - antagonists & inhibitors Nerve Tissue Proteins - biosynthesis Neurodegeneration Neurology Neurons Neurons - drug effects Neurons - metabolism Neurons - pathology Neurosciences Oligodendroglia - drug effects Oligodendroglia - metabolism Oligodendroglia - pathology Pharmacotherapy Proteins Psychiatry Psychopharmacology Rodents Signal Transduction Spinal cord Studies Epidermal Growth Factor Receptor Cuprizone Experimental Autoimmune Encephalomyelitis Myelin Basic Protein Magnetization Transfer Ratio
ISSN:	1172-7047, 1179-1934, 1179-1934
Online Access:	Get full text
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-General Information-1 content type line 14 ObjectType-Feature-3 ObjectType-Article-1 ObjectType-Feature-2 ObjectType-Review-3 content type line 23 ObjectType-Feature-1
ISSN:	1172-7047 1179-1934 1179-1934
DOI:	10.1007/s40263-013-0068-8