| Autor: |
Martina Colognesi, Atea Shkodra, Daniela Gabbia, Hibiki Kawamata, Paolo L. Manfredi, Giovanni Manfredi, Sara De Martin |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Frontiers in Neurology, Vol 15 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1664-2295 |
| DOI: |
10.3389/fneur.2024.1384829 |
| Popis: |
IntroductionThe pathogenesis of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease caused by the demise of motor neurons has been linked to excitotoxicity caused by excessive calcium influx via N-methyl-D-aspartate receptors (NMDARs), suggesting that uncompetitive NMDAR antagonism could be a strategy to attenuate motor neuron degeneration. REL-1017, the dextro-isomer of racemic methadone, is a low-affinity uncompetitive NMDAR antagonist. Importantly, in humans REL-1017 has shown excellent tolerability in clinical trials for major depression.MethodsHere, we tested if REL-1017 improves the disease phenotypes in the G93A SOD1 mouse, a well-established model of familial ALS, by examining survival and motor functions, as well as the expression of genes and proteins involved in neuroplasticity.ResultsWe found a sex-dependent effect of REL-1017 in G93A SOD1 mice. A delay of ALS symptom onset, assessed as 10%-decrease of body weight (p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
