Abstract:
:Huntington disease (HD) is a genetic neurodegenerative disorder for which there is currently no cure and no way to stop or even slow the brain changes it causes. In the present study, we aimed to investigate whether FTY720, the first approved oral therapy for multiple sclerosis, may be effective in HD models and eventually constitute an alternative therapeutic approach for the treatment of the disease. Here, we utilized preclinical target validation paradigms and examined the in vivo efficacy of chronic administration of FTY720 in R6/2 HD mouse model. Our findings indicate that FTY720 improved motor function, prolonged survival and reduced brain atrophy in R6/2 mice. The beneficial effect of FTY720 administration was associated with a significant strengthening of neuronal activity and connectivity and, with reduction of mutant huntingtin aggregates, and it was also paralleled by increased phosphorylation of mutant huntingtin at serine 13/16 residues that are predicted to attenuate protein toxicity.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Di Pardo A,Amico E,Favellato M,Castrataro R,Fucile S,Squitieri F,Maglione Vdoi
10.1093/hmg/ddt615subject
Has Abstractpub_date
2014-05-01 00:00:00pages
2251-65issue
9eissn
0964-6906issn
1460-2083pii
ddt615journal_volume
23pub_type
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