Huntington disease (HD), a neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene, remains without a treatment to modify the course of the illness. Lithium, a drug widely used for the treatment of bipolar disorder, has been shown to exert neuroprotective effects in a number of models of neurological disease but may have various toxic effects at conventional therapeutic doses. We examined whether NP03, a novel low-dose lithium microemulsion, would improve the disease phenotypes in the YAC128 mouse model of HD. We demonstrate that NP03 improves motor function, ameliorates the neuropathological deficits in striatal volume, neuronal counts, and DARPP-32 expression, and partially rescues testicular atrophy in YAC128 mice. These positive effects were accompanied by improvements in multiple biochemical endpoints associated with the pathogenesis of HD, including normalization of caspase-6 activation and amelioration of deficits in BDNF levels, and with no lithium-related toxicity. Our findings demonstrate that NP03 ameliorates the motor and neuropathological phenotypes in the YAC128 mouse model of HD, and represents a potential therapeutic approach for HD.
NP03, a novel low-dose lithium formulation, is neuroprotective in the YAC128 mouse model of Huntington disease / M.A. Pouladi, E. Brillaud, Y. Xie, P. Conforti, R.K. Graham, D.E. Ehrnhoefer, S. Franciosi, W. Zhang, P. Poucheret, E. Compte, J.C. Maurel, C. Zuccato, E. Cattaneo, C. Néri, M.R. Hayden. - In: NEUROBIOLOGY OF DISEASE. - ISSN 0969-9961. - 48:3(2012 Dec), pp. 282-289.
|Titolo:||NP03, a novel low-dose lithium formulation, is neuroprotective in the YAC128 mouse model of Huntington disease|
|Parole Chiave:||Huntington disease; Transgenic mouse model; Lithium; Caspase-6; BDNF; GSK-3; Tau|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||dic-2012|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.nbd.2012.06.026|
|Appare nelle tipologie:||01 - Articolo su periodico|