| First Author | Da Cruz S | Year | 2012 |
| Journal | Cell Metab | Volume | 15 |
| Issue | 5 | Pages | 778-86 |
| PubMed ID | 22560226 | Mgi Jnum | J:184777 |
| Mgi Id | MGI:5426308 | Doi | 10.1016/j.cmet.2012.03.019 |
| Citation | Da Cruz S, et al. (2012) Elevated PGC-1alpha activity sustains mitochondrial biogenesis and muscle function without extending survival in a mouse model of inherited ALS. Cell Metab 15(5):778-86 |
| abstractText | The transcriptional coactivator PGC-1alpha induces multiple effects on muscle, including increased mitochondrial mass and activity. Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, adult-onset neurodegenerative disorder characterized by selective loss of motor neurons and skeletal muscle degeneration. An early event is thought to be denervation-induced muscle atrophy accompanied by alterations in mitochondrial activity and morphology within muscle. We now report that elevation of PGC-1alpha levels in muscles of mice that develop fatal paralysis from an ALS-causing SOD1 mutant elevates PGC-1alpha-dependent pathways throughout disease course. Mitochondrial biogenesis and activity are maintained through end-stage disease, accompanied by retention of muscle function, delayed muscle atrophy, and significantly improved muscle endurance even at late disease stages. However, survival was not extended. Therefore, muscle is not a primary target of mutant SOD1-mediated toxicity, but drugs increasing PGC-1alpha activity in muscle represent an attractive therapy for maintaining muscle function during progression of ALS. |
