RGD Reference Report - Akt signal transduction dysfunction in Parkinson's disease. - Rat Genome Database

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Akt signal transduction dysfunction in Parkinson's disease.

Authors: Timmons, S  Coakley, MF  Moloney, AM  O' Neill, C 
Citation: Timmons S, etal., Neurosci Lett. 2009 Dec 18;467(1):30-5. Epub 2009 Oct 1.
RGD ID: 5509074
Pubmed: PMID:19800394   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neulet.2009.09.055   (Journal Full-text)

Significant attention has been drawn to the potential role of defective PI3-kinase-Akt (PKB) signalling in Parkinson's disease (PD) neurodegeneration and to the possibility that activation of Akt may provide neuroprotection in PD. However, little knowledge exists on the integrity of the Akt system in PD. Results of the present study show diminished levels of both total and active phospho(Ser473)-Akt in the brain in PD. This was evident by western blot analysis of midbrain fractions from PD compared to non-PD control brain, but more specifically by immunofluorescence microscopy of the substantia nigra pars compacta (SNpc). Here, double immunofluorescence microscopy found Akt and phospho(Ser473)-Akt to be expressed at high levels in tyrosine hydroxylase (TH) immunopositive dopaminergic neurons in control human brain. Selective loss of these neurons was accompanied by a marked decrease of Akt and phospho(Ser473)-Akt expression in the PD brain, however Akt and active phospho(Ser473)-Akt are still evident in degenerating dopaminergic neurons in the disease. This suggests that it may be possible to target neuronal Akt in advanced PD. Converse to the marked loss of neuronal Akt in PD, increased Akt and phospho(Ser473)-Akt levels were observed in small non-TH positive cells in PD SNpc, whose increased number and small nuclear size indicate they are glia. These findings implicate defective Akt as a putative signalling pathway linked to loss of dopaminergic neurons in PD.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AKT1HumanParkinson's disease  IEP protein:altered expression:brainRGD 
Akt1RatParkinson's disease  ISOAKT1 (Homo sapiens)protein:altered expression:brainRGD 
Akt1MouseParkinson's disease  ISOAKT1 (Homo sapiens)protein:altered expression:brainRGD 

Objects Annotated

Genes (Rattus norvegicus)
Akt1  (AKT serine/threonine kinase 1)

Genes (Mus musculus)
Akt1  (thymoma viral proto-oncogene 1)

Genes (Homo sapiens)
AKT1  (AKT serine/threonine kinase 1)


Additional Information