OXIDATIVE STRESS IN HUNTINGTON DISEASE, PROTECTION BY THE hMTH1 HYDROLASE

Huntington’s disease (HD) is a devastating neurological disease for which no effective treatments are available to date. Although the mechanisms by which the gene defect responsible for HD leads to neuronal degeneration remains incompletely understood, the involvement of oxidative stress is well established. The aim of this project is to evaluate whether hMTH1, an enzyme that protects DNA from oxidative damage, could represent a target to develop neuroprotective strategies for HD. We have recently developed a transgenic mouse which over-expresses hMTH1 and is more resistant to the toxic effects of 3-nitropropionic acid (a toxin that induces HD-like alterations in mice). In this project we will evaluate whether the neuroprotective effects of hMTH1 overexpression are also evident in mice expressing the HD mutation, and the mechanisms responsible for neuroprotection will be investigated.