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Carvedilol protection against endogenous A?-induced neurotoxicity in N2a cells.


ABSTRACT: Mutations in amyloid precursor protein (APP) and presenilin1 result in overproduction and accumulation of ?-amyloid (A?) peptide, which has been shown to play an important role in Alzheimer's disease (AD) pathogenesis. Carvedilol, a nonselective ?-adrenergic receptor blocker used for treatment for heart failure and hypertension, has displayed its neuroprotective capacity due to its antioxidant property. In this study, we investigated whether Carvedilol has a neuronal protective effect against endogenous A? neurotoxicity in mouse Neuro2a (N2a) cells transfected with Swedish amyloid precursor protein (Swe-APP) mutant and Presenilin exon9 deletion mutant (N2a/Swe.D9). Elevated levels of reactive oxygen species (ROS), protein carbonyls, and 4-HNE were found in N2a/Swe.D9 cells, which were ameliorated by administration of Carvedilol in a dose-dependent manner. In addition, the levels of ATP and mitochondrial membrane potential were reduced in N2a/Swe.D9 cells, which were restored by treatment with Carvedilol. N2a/Swe.D9 cells displayed increased vulnerability to H2O2-induced cell death and apoptosis, which could be attenuated by Carvedilol. Mechanistically, we found that Carvedilol prevented apoptosis signals through reducing cytochrome C release and the level of cleaved caspase-3. Taken together, our findings suggest a possible use of Carvedilol in AD treatment.

SUBMITTER: Liu J 

PROVIDER: S-EPMC6045552 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Carvedilol protection against endogenous Aβ-induced neurotoxicity in N2a cells.

Liu Jia J   Wang Min M  

Cell stress & chaperones 20180212 4


Mutations in amyloid precursor protein (APP) and presenilin1 result in overproduction and accumulation of β-amyloid (Aβ) peptide, which has been shown to play an important role in Alzheimer's disease (AD) pathogenesis. Carvedilol, a nonselective β-adrenergic receptor blocker used for treatment for heart failure and hypertension, has displayed its neuroprotective capacity due to its antioxidant property. In this study, we investigated whether Carvedilol has a neuronal protective effect against en  ...[more]

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