PGC-1α PROTECTS NEURONS AND ALTERS DISEASE PROGRESSION IN AN AMYOTROPHIC LATERAL SCLEROSIS MOUSE MODEL

Introduction: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. We sought to determine whether peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) would have a beneficial effect on this disease. Methods: PGC-1 alpha transgenic mice were crossed with SOD1 mutant G93A DL mice. Results: We observed a moderate but non-significant increase in average lifespan in PGC-1 alpha/G93A DL mice, as compared with G93A DL mice (292 +/- 3 days vs. 274 +/- 7 days). Although the onset of ALS was not altered, progression of the disease was significantly slower (similar to 34% increase in duration) in the PGC-1 alpha/G93A DL mice. These mice also exhibited markedly improved performance on the rotarod test, and the improved motor activity was associated with a decreased loss of motor neurons and less degeneration of neuromuscular junctions. Conclusion: A sustained level of excitatory amino acid transporter protein 2 (EAAT2) in astrocytes of the PGC-1 alpha/G93A DL mice may contribute to neuronal protection. Muscle Nerve 44: 947-956, 2011