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

作     者：Michael F.Wangler Lawrence T.Reiter Georgianna Zimm Jennifer Trimble-Morgan Jane Wu Ethan Bier 

作者机构：Department of BiologyUniversity of California at San DiegoSan DiegoCA 92093USA Department of Molecular and Human GeneticsBaylor College of MedicineOne Baylor PlazaHoustonTX 77030USA Department of NeurologyUniversity of Tennessee Health Science CenterMemphisTN 38163USA Saddleback College28000 Marguerite ParkwayMission ViejoCalifornia 92692USA Department of Neurology and Center for Genetic MedicineNorthwestern UniversityChicagoIL 60611USA 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2011年第2卷第7期

页      面：554-563页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：NHGRI NIH HHS [R01 HG011795] Funding Source: Medline NIAID NIH HHS [R01 AI070654] Funding Source: Medline NINDS NIH HHS [K08 NS076547] Funding Source: Medline 

主　　题：Presenilin Alzheimer’s disease peroxiredoxin Notch 

摘      要：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.