| First Author | Schiaffino L | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 12875 |
| PubMed ID | 30150770 | Mgi Jnum | J:278056 |
| Mgi Id | MGI:6356117 | Doi | 10.1038/s41598-018-30659-4 |
| Citation | Schiaffino L, et al. (2018) Acetylation state of RelA modulated by epigenetic drugs prolongs survival and induces a neuroprotective effect on ALS murine model. Sci Rep 8(1):12875 |
| abstractText | Dysregulation in acetylation homeostasis has been implicated in the pathogenesis of the amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. It is known that the acetylation of transcriptional factors regulates their activity. The acetylation state of NF-kB RelA has been found to dictate the neuroprotective versus the neurotoxic effect of p50/RelA. Here we showed that the pro-apoptotic acetylation mode of RelA, involving a general lysine deacetylation of the subunit with the exclusion of the lysine 310, is evident in the lumbar spinal cord of SOD1(G93A) mice, a murine model of ALS. The administration of the HDAC inhibitor MS-275 and the AMPK/sirtuin 1 activator resveratrol restored the normal RelA acetylation in SOD1(G93A) mice. The SOD1(G93A) mice displayed a 3 weeks delay of the disease onset, associated with improvement of motor performance, and 2 weeks increase of lifespan. The epigenetic treatment rescued the lumbar motor neurons affected in SOD1(G93A) mice, accompanied by increased levels of protein products of NF-kB-target genes, Bcl-xL and brain-derived neurotrophic factor. In conclusion, we here demonstrate that MS-275 and resveratrol restore the acetylation state of RelA in the spinal cord, delaying the onset and increasing the lifespan of SOD1(G93A) mice. |
