Increased Mammalian Target of Rapamycin Signaling Contributes to the Accumulation of Protein Oxidative Damage in a Mouse Model of Down's Syndrome.

This study analyzed mTOR signaling in Ts65Dn mice, a model of DS, at 6 and 12 months of age compared with euploid mice showing the early aberrant hyperphosphorylation of mTOR coupled with the reduction of autophagosome formation. Moreover, the evaluation of protein oxidation shows an increase in protein nitration and protein-bound 4-hydroxynonenal in 12-month-old Ts65Dn mice suggesting the potential involvement of altered autophagy in the buildup of protein oxidative damage. In addition, data obtained on cell culture support the protective role of autophagy in reducing protein oxidation. Key Messages: Overall, this study provides further evidence for the role of mTOR hyperactivation and reduced autophagy in the accumulation of protein oxidative damage during DS and AD pathologies. PMID: 26606243 [PubMed - as supplied by publisher]
Source: Neuro-Degenerative Diseases - Category: Neurology Authors: Tags: Neurodegener Dis Source Type: research