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                                       Details van artikel 10 van 18 gevonden artikelen
 
 
  Isoform Specific Amyloid-β Protein Precursor Metabolism
 
 
Titel: Isoform Specific Amyloid-β Protein Precursor Metabolism
Auteur: Henriques, Ana Gabriela
Vieira, Sandra Isabel
Rebelo, Sandra
Domingues, Sara C.T.S.
da Cruz e Silva, Edgar F.
da Cruz e Silva, Odete A.B.
Verschenen in: Journal of Alzheimer's disease
Paginering: Jaargang 11 (2007) nr. 1 pagina's 85-95
Jaar: 2007-03-15
Inhoud: Alzheimer's amyloid-β protein precursor (AβPP) can occur in different isoforms, among them AβPP_{751}, which is the most abundant isoform in non-neuronal tissues, and AβPP_{695}, often referred to as the neuronal isoform. However, few isoform-specific roles have been addressed. In the work here described, AβPP isoforms, both endogenous and as cDNA fusions with green fluorescent protein (GFP), were used to permit isoform-specific monitoring in terms of intracellular processing and targeting. Differences were particularly marked in the turnover rates of the immature isoforms, with AβPP_{751} having a faster turnover rate than AβPP_{695} (0.8 h and 1.2 h respectively for endogenous proteins and 1.1 h and 2.3 h for transfected proteins). Hence, AβPP_{751} matures faster. Additionally, AβPP_{751} responded to both okadaic acid (OA) and phorbol 12-myristate 13-acetate (PMA), as determined by sAβPP production, with PMA inducing a more robust response. For the AβPP_{695} isoform, however, although PMA produced a strong response, OA failed to elicit such an induction in sAβPP production, implicating isoform specificity in phosphorylation regulated events. In conclusion, it seems that the AβPP_{695} isoform is processed/metabolized at a slower rate and responds differently to OA when compared to the AβPP_{751} isoform. The relevance of isoform-specific processing in relation to Alzheimer's disease needs to be further investigated, given the predominance of the AβPP_{695} isoform in neuronal tissues and isoform-specific alterations in expression levels associated with the pathology.
Uitgever: IOS Press
Bronbestand: Elektronische Wetenschappelijke Tijdschriften
 
 

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