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Physical Sciences and Mathematics Commons

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Chemistry Faculty Publications

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Full-Text Articles in Physical Sciences and Mathematics

Restoration Of Aberrant Mtor Signaling By Intranasal Rapamycin Reduces Oxidative Damage: Focus On Hne-Modified Proteins In A Mouse Model Of Down Syndrome, Fabio Di Domenico, Antonella Tramutola, Eugenio Barone, Chiara Lanzillotta, Olivia Defever, Andrea Arena, Ilaria Zuliani, Cesira Foppoli, Federica Iavarone, Federica Vincenzoni, Massimo Castagnola, D. Allan Butterfield, Marzia Perluigi Mar 2019

Restoration Of Aberrant Mtor Signaling By Intranasal Rapamycin Reduces Oxidative Damage: Focus On Hne-Modified Proteins In A Mouse Model Of Down Syndrome, Fabio Di Domenico, Antonella Tramutola, Eugenio Barone, Chiara Lanzillotta, Olivia Defever, Andrea Arena, Ilaria Zuliani, Cesira Foppoli, Federica Iavarone, Federica Vincenzoni, Massimo Castagnola, D. Allan Butterfield, Marzia Perluigi

Chemistry Faculty Publications

Increasing evidences support the notion that the impairment of intracellular degradative machinery is responsible for the accumulation of oxidized/misfolded proteins that ultimately results in the deposition of protein aggregates. These events are key pathological aspects of “protein misfolding diseases”, including Alzheimer disease (AD). Interestingly, Down syndrome (DS) neuropathology shares many features with AD, such as the deposition of both amyloid plaques and neurofibrillary tangles. Studies from our group and others demonstrated, in DS brain, the dysfunction of both proteasome and autophagy degradative systems, coupled with increased oxidative damage. Further, we observed the aberrant increase of mTOR signaling and of its …


Intranasal Rapamycin Ameliorates Alzheimer-Like Cognitive Decline In A Mouse Model Of Down Syndrome, Antonella Tramutola, Chiara Lanzillotta, Eugenio Barone, Andrea Arena, Ilaria Zuliani, Luciana Mosca, Carla Blarzino, D. Allan Butterfield, Marzia Perluigi, Fabio Di Domenico Nov 2018

Intranasal Rapamycin Ameliorates Alzheimer-Like Cognitive Decline In A Mouse Model Of Down Syndrome, Antonella Tramutola, Chiara Lanzillotta, Eugenio Barone, Andrea Arena, Ilaria Zuliani, Luciana Mosca, Carla Blarzino, D. Allan Butterfield, Marzia Perluigi, Fabio Di Domenico

Chemistry Faculty Publications

Background: Down syndrome (DS) individuals, by the age of 40s, are at increased risk to develop Alzheimer-like dementia, with deposition in brain of senile plaques and neurofibrillary tangles. Our laboratory recently demonstrated the disturbance of PI3K/AKT/mTOR axis in DS brain, prior and after the development of Alzheimer Disease (AD). The aberrant modulation of the mTOR signalling in DS and AD age-related cognitive decline affects crucial neuronal pathways, including insulin signaling and autophagy, involved in pathology onset and progression. Within this context, the therapeutic use of mTOR-inhibitors may prevent/attenuate the neurodegenerative phenomena. By our work we aimed to rescue mTOR signalling …