Suppression of Adenosine 2a Receptor (A2aR)-Mediated Adenosine Signaling Improves Disease Phenotypes in a Mouse Model of Amyotrophic Lateral Sclerosis.

Suppression of Adenosine 2a Receptor (A2aR)-Mediated Adenosine Signaling Improves Disease Phenotypes in a Mouse Model of Amyotrophic Lateral Sclerosis. Exp Neurol. 2015 Mar 13; Authors: Ng SK, Higashimori H, Tolman M, Yang Y Abstract Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease in which the majority of upper and lower motor neurons are degenerated. Despite intensive efforts to identify drug targets and develop neuroprotective strategies, effective therapeutics for ALS remains unavailable. The identification and characterization of novel targets and pathways remain crucial in the development of ALS therapeutics. Adenosine is a major neuromodulator that actively regulates synaptic transmission. Interestingly, adenosine levels are significantly elevated in the cerebrospinal fluid (CSF) of progressing human ALS patients. In the current study, we showed that adenosine 2a receptor (A2aR), but not adenosine 1 receptor (A1R), is highly enriched in spinal (motor) neurons. A2aR expression is also selectively increased at the symptomatic onset in the spinal cords of SOD1G93A mice and end-stage human ALS spinal cords. Interestingly, we found that direct adenosine treatment is sufficient to induce embryonic stem cell-derived motor neuron (ESMN) cell death in cultures. Subsequent pharmacological inhibition and partial genetic ablation of A2aR (A2aR(+/-)) significantly protect ESMN from SOD1G93A(+) astrocyt...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research