Notas:
|
The molecular bases that account for the preferential neurodegeneration of striatal mediumsized
spiny neurons (MSNs) in Huntington’s Disease (HD) are still unknown, and different
mechanisms have been proposed to contribute to the neurodegenerative process.
These include mitochondrial dysfunction and metabolic impairment, transcriptional
dysregulation, altered expression of trophic factors, dopamine toxicity, oxidative stress, and
changes in autophagy, and huntingtin (htt) phosphorylation. In addition, excitotoxicity
through the overactivation of N-methyl-D-aspartate (NMDA) receptors (NMDARs) has also
been proposed to contribute to the preferential loss of these neurons (for review see
Ehrnhoefer et al., 2011; Jin & Johnson, 2010; Perez-Navarro et al., 2006; Renna et al., 2010;
Rosenstock et al., 2010; Weir et al., 2011).
Some of these mechanisms are controlled by the attachment/removal of phosphate groups
through the action of protein kinases and protein phosphatases, respectively. Therefore,
alterations in their levels/activity in the presence of mutant htt (mhtt) can impact on cell
survival... |