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Antioxidant proteins TSA and PAG interact synergistically with Presenilin to modulate Notch signaling in Drosophila

Protein & Cell 2011年第7期2卷 554-563页

作者： Michael F.Wangler Lawrence T.Reiter Georgianna Zimm Jennifer Trimble-Morgan Jane Wu Ethan Bier Department of Biology University of California at San DiegoSan DiegoCA 92093USA Department of Molecular and Human Genetics Baylor College of MedicineOne Baylor PlazaHoustonTX 77030USA Department of Neurology University of Tennessee Health Science CenterMemphisTN 38163USA saddleback college 28000 Marguerite ParkwayMission ViejoCalifornia 92692USA Department of Neurology and Center for Genetic Medicine Northwestern UniversityChicagoIL 60611USA

Alzheimer’s disease(AD)pathogenesis is characterized by senile plaques in the brain and evidence of oxidative *** stress may precede plaque formation in AD;however,the link between oxidative damage and plaque formation remains *** are transmembrane proteins in which mutations lead to accelerated plaque formation and early-onset familial Alzheimer’s *** physically interact with two antioxidant enzymes thiol-specific antioxidant(TSA)and proliferation-associated gene(PAG)of the peroxiredoxin *** functional consequences of these interactions are *** the current study we expressed a presenilin transgene in Drosophila wing and sensory organ precursors of the *** caused phenotypes typical of Notch signaling loss-of-function *** found that while expression of TSA or PAG alone produced no phenotype,co-expression of TSA and PAG with presenilin led to an enhanced Notch loss-offunction *** phenotype was more severe and more penetrant than that caused by the expression of Psn *** order to determine whether these phenotypes were indeed affecting Notch signaling,this experiment was performed in a genetic background carrying an activated Notch(Abruptex)*** phenotypes were almost completely rescued by this activated Notch *** results link peroxiredoxins with the in vivo function of Presenilin,which ultimately connects two key pathogenetic mechanisms in AD,namely,antioxidant activity and plaque formation,and raises the possibility of a role for peroxiredoxin family members in Alzheimer’s pathogenesis.

关键词： Presenilin Alzheimer’s disease peroxiredoxin Notch

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