Rapamycin Protects Against Neuron Death in in Vitro and in Vivo Models of Parkinson's Disease

Overview

Journal J Neurosci

Specialty Neurology

Date 2010 Jan 22

PMID 20089925

Citations 240

Authors

Cristina Malagelada

Zong Hao Jin

Vernice Jackson-Lewis

Serge Przedborski

Lloyd A Greene

Affiliations

Soon will be listed here.

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.

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