RGD Reference Report - Rapamycin protects against neuron death in in vitro and in vivo models of Parkinson's disease. - Rat Genome Database

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

Authors: Malagelada, C  Jin, ZH  Jackson-Lewis, V  Przedborski, S  Greene, LA 
Citation: Malagelada C, etal., J Neurosci. 2010 Jan 20;30(3):1166-75. doi: 10.1523/JNEUROSCI.3944-09.2010.
RGD ID: 10040992
Pubmed: PMID:20089925   (View Abstract at PubMed)
PMCID: PMC2880868   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.3944-09.2010   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MTORHumanParkinsonism treatmentISOMtor (Mus musculus) RGD 
MtorRatParkinsonism treatmentISOMtor (Mus musculus) RGD 
MtorMouseParkinsonism treatmentIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mtor  (mechanistic target of rapamycin kinase)

Genes (Mus musculus)
Mtor  (mechanistic target of rapamycin kinase)

Genes (Homo sapiens)
MTOR  (mechanistic target of rapamycin kinase)


Additional Information