“…Furthermore, these models should prove useful for the investigation of neurodegenerative mechanisms characterized by delayed onset and slow progression over years or decades. Indeed, oxidative stress and mitochondrial dysfunction, as well as activation of autophagy in several of the major human neurodegenerative disorders, including Alzheimer's disease (Nixon et al, 2000;Hirai et al, 2001;Perry et al, 2002), Parkinson's disease (Anglade et al, 1997;Meredith et al, 2002), and Huntington's disease (Kegel et al, 2000), have been reported repeatedly, although their role in these pathologies is still discussed. The novel spatiotemporally controlled conditional gene-targeting approach that we have used is particularly adapted to study the mechanisms of lateonset and slowly progressive neurodegeneration and is amenable to large experimental flexibility through modulation at will of the timing of induction.…”