Role of CCR2 in ALS disease
Association between Expression of Chemokine Receptor-2 (CCR2) and Amyotrophic Lateral Sclerosis (ALS) Patients of North India.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which is characterized by participation of inflammatory cascade. These inflammatory changes are strongly regulated by interaction of chemokine ligand-2 (CCL2), a small chemokine belongs to C-C subfamily with its receptor chemokine receptor-2 (CCR2). In our earlier studies we have reported elevated chemokine ligand-2 (CCL2) in Indian ALS patients. We further analysed chemokine receptor-2 (CCR2) in these ALS patients. Indian sporadic ALS patients (n = 50) and control (40) were included on the basis of El Escorial criteria. CCR2 expression in peripheral blood mononuclear cells (PBMCs) was valuated using Flow Cytometry and Real Time Polymerase Chain Reaction (PCR). Flow Cytometry revealed significantly reduced CCR2 expressing PBMCs in the ALS patients, decline was more significant in limb onset ALS when compared to bulbar onset ALS. PBMCs from ALS patients showed substantial down-regulation of CCR2 mRNA. When compared with bulbar onset ALS CCR2 mRNA expression was found to be decreased among limb ALS patients. Further, the count of CCR2+ PBMCs and CCR2 mRNA transcript in PBMCs was significantly lower in severe and moderate ALS as compared to ALS patients with mild impairments. This downregulation of CCR2 expression in PBMCs suggests its role in etiology of ALS pathogenesis. It can be postulated that reduction in PBMCs CCR2 may result in decreased infiltration of leukocytes at the site of degeneration as a compensatory response to ALS.
Gupta P K, Prabhakar S, Sharma N K, Anand A. Possible Association between Expression of Chemokine Receptor-2 (CCR2) and Amyotrophic Lateral Sclerosis (ALS) Patients of North India. PLoS ONE 7(6): e38382. doi:10.1371/journal.pone.0038382