LINGO-1 antagonists as therapy for multiple sclerosis: in vitro and in vivo evidence.
ABSTRACT 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.
This article provides an overview of the available data on the effects of LINGO-1 antagonists on oligodendrocyte differentiation and remyelination.
LINGO-1 is a potential target for neuroprotective therapy in that antagonists may promote remyelination in diseases such as MS.
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ABSTRACT: Spontaneous intracerebral hemorrhage (ICH) represents about 15% of all strokes and is associated with high mortality rates. Our aim was to identify the gene expression changes and biological pathways altered in the brain following ICH. Twelve brain samples were obtained from four deceased patients who suffered an ICH including perihematomal tissue (PH) and the corresponding contralateral white (CW) and grey (CG) matter. Affymetrix GeneChip platform for analysis of over 47,000 transcripts was conducted. Microarray Analysis Suite 5.0 was used to process array images and the Ingenuity Pathway Analysis System was used to analyze biological mechanisms and functions of the genes. We identified 468 genes in the PH areas displaying a different expression pattern with a fold change between -3.74 and +5.16 when compared to the contralateral areas (291 overexpressed and 177 underexpressed). The top genes which appeared most significantly overexpressed in the PH areas codify for cytokines, chemokines, coagulation factors, cell growth and proliferation factors while the underexpressed codify for proteins involved in cell cycle or neurotrophins. Validation and replication studies at gene and protein level in brain samples confirmed microarray results. The genomic responses identified in this study provide valuable information about potential biomarkers and target molecules altered in the perihematomal regions.PLoS ONE 01/2011; 6(2):e16750. · 4.09 Impact Factor