The toxicity of N-methylated Sample Clauses

The toxicity of N-methylated βCs The toxicity of the N-methylated βCs has been studied extensively (Xxxxxxx et al. 1989, Xxxxxxxxx et al. 1998, Xxxxxx et al. 2004, Xxxxxx et al. 2006, Xxxxxxxx et al. 2006, Xxxxxxxx et al. 2007). While 2N-methylation has been shown to confer toxic properties and dopaminergic neuron specificity to most βCs, 9N-methylation of 2- MeNH appears to be a crucial step in toxicity potentiation as 2,9-diMeNH has been shown to be markedly more toxic than 2-MeNH in Neuro 2A cells (Bonnet et al. 2004), DAT-transfected and wild type human embryonic kidney (HEK) cells (Xxxxxxxx et al. 2007) and primary dopaminergic neurons (Xxxxxx et al. 2006). In fact, 2,9-diMeNH has shown comparable toxicity to MPP+ with a reduced reliance on DAT (Xxxxxx et al. 2004, Xxxxxx et al. 2006, Xxxxxxxx et al. 2007). Despite a lowered DAT dependency relative to MPP+, 2,9-diMeNH has been shown to be selective for dopaminergic neurons compared with other neurons and non- neuronal cells (Xxxxxxxx et al. 2006). N-methylated βCs, like MPP+, are principally thought to act via inhibition of CxI of the mitochondrial respiratory chain, although weaker inhibition at complexes II and III have also been reported (Albores et al. 1990, Xxxxxxx et al. 1992, Xxxxxx et al.