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J Neurosci. 2010 Jan 20;30(3):1166-75. doi: 10.1523/JNEUROSCI.3944-09.2010.

Rapamycin protects against neuron death in in vitro and in vivo models of Parkinson's disease.

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  • 1Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA. cm2273@columbia.edu

Abstract

We report that rapamycin, an allosteric inhibitor of certain but not all actions of the key cellular kinase mammalian target of rapamycin (mTOR), protects neurons from death in both cellular and animal toxin models of Parkinson's disease (PD). This protective action appears to be attributable to blocked translation of RTP801/REDD1/Ddit4, a protein that is induced in cell and animal models of PD and in affected neurons of PD patients and that causes neuron death by leading to dephosphorylation of the survival kinase Akt. In support of this mechanism, in PD models, rapamycin spares phosphorylation of Akt at a site critical for maintenance of its survival-promoting activity. The capacity of rapamycin to provide neuroprotection in PD models appears to arise from its selective suppression of some but not all actions of mTOR, as indicated by the contrasting finding that Torin1, a full catalytic mTOR inhibitor, is not protective and induces Akt dephosphorylation and neuron death.

PMID:
20089925
[PubMed - indexed for MEDLINE]
PMCID:
PMC2880868
Free PMC Article

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