RGD Reference Report - Activation of ataxia telangiectasia muted under experimental models and human Parkinson's disease. - Rat Genome Database

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Activation of ataxia telangiectasia muted under experimental models and human Parkinson's disease.

Authors: Camins, A  Pizarro, JG  Alvira, D  Gutierrez-Cuesta, J  De la Torre, AV  Folch, J  Sureda, FX  Verdaguer, E  Junyent, F  Jordan, J  Ferrer, I  Pallas, M 
Citation: Camins A, etal., Cell Mol Life Sci. 2010 Nov;67(22):3865-82. doi: 10.1007/s00018-010-0408-5. Epub 2010 May 26.
RGD ID: 10053605
Pubmed: PMID:20502937   (View Abstract at PubMed)
DOI: DOI:10.1007/s00018-010-0408-5   (Journal Full-text)

In the present study we demonstrated that neurotoxin MPP(+)-induced DNA damage is followed by ataxia telangiectasia muted (ATM) activation either in cerebellar granule cells (CGC) or in B65 cell line. In CGC, the selective ATM inhibitor KU-55933 showed neuroprotective effects against MPP(+)-induced neuronal cell loss and apoptosis, lending support to the key role of ATM in experimental models of Parkinson's disease. Likewise, we showed that knockdown of ATM levels in neuroblastoma B65 cells using an ATM-specific siRNA attenuates the phosphorylation of retinoblastoma protein without affecting other cell-cycle proteins involved in the G(0)/G(1) cell-cycle phase. Moreover, we demonstrated DNA damage, in human brain samples of PD patients. These findings support a model in which MPP(+) leads to ATM activation with a subsequent DNA damage response and activation of pRb. Therefore, this study demonstrates a new link between DNA damage by MPP(+) and cell-cycle re-entry through retinoblastoma protein phosphorylation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Parkinson's disease  IDA 10053605protein:increased serine phosphorylation:cingulate gyrus RGD 
Parkinson's disease  ISOATM (Homo sapiens)10053605; 10053605protein:increased serine phosphorylation:cingulate gyrus RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of neuron apoptotic process  IMP 10053605 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Atm  (ATM serine/threonine kinase)

Genes (Mus musculus)
Atm  (ataxia telangiectasia mutated)

Genes (Homo sapiens)
ATM  (ATM serine/threonine kinase)


Additional Information