Targeting the Nogo Receptor Complex in Diseases of the Central Nervous System
Abstract:After injury to the central nervous system intrinsic factors such as myelin associated inhibitory factors inhibit cellular and axonal regeneration resulting in permanent disability. Three of these factors (Nogo-A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein) bind to a common receptor: the Nogo-66 receptor (NgR1). NgR1 is expressed mainly on neurons and is usually associated in a trimolecular complex. The second member of the complex, LINGO-1, is often connected to NgR1 function and is further found to function independently as a negative regulator of oligodendrocyte proliferation and differentiation. The third member of the NgR complex is either the p75 neurotrophin receptor, TROY, or an as yet unidentified co-receptor. Targeting of factors contained in this complex has been described to lead to the promotion of neurite outgrowth, oligodendrocyte proliferation and differentiation and inhibition of cell death. In the current review, we aim to describe the mechanisms of action of the chemical and biological compounds used in targeting NgR1 and LINGO-1. This will be achieved using three examples: blocking of ligand binding to NgR1 in treatment of spinal cord injury, antibody-mediated inhibition of LINGO-1 to promote oligodendrocyte differentiation in multiple sclerosis, and the use of soluble NgR1 to sequester Abeta peptide in the periphery in Alzheimer's disease.
Keywords: Alzheimer's disease; B lymphocyte stimulator; Interferon-s; LINGO-1; Multiple Sclerosi; Parkinson's disease; Purkinje cells; Schwann cell grafts; alka-line phosphatase (AP); amyloid peptide; blood-brain barrier; central nervous system intrinsic; chondroitin sulphate proteoglycans; corticospinal tract; erythropoietin; glatiramir acetate; glucocorticosteroids; glycoprotein; glycosylphosphatidylinositol; guanosine triphosphatase; hippocampal neurons; hybridization; immunohistochemis-try; intravenous steroids; minocyclin; multiple sclerosis; mutagenesis; myelin associated inhibitory factors; myelination; neurotrophin receptor; nogo receptor; olfactory nervous system; oli-godendrocyte; oligodendrocyte mye-lin glycoprotein; oligodendrocyte precursor; proteolipid protein; remyelination; sclerosis; serotonergic axon; spinal cord injury; thoracic spinal cord
Document Type: Research Article
Publication date: January 1, 2011
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