Cell Stress and Chaperones

, Volume 23, Issue 4, pp 695–702 | Cite as

Carvedilol protection against endogenous Aβ-induced neurotoxicity in N2a cells

  • Jia Liu
  • Min WangEmail author
Original Paper


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 endogenous Aβ 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.


Alzheimer’s disease Amyloid β Carvedilol Oxidative stress Apoptosis 

Supplementary material

12192_2018_881_Fig6_ESM.gif (114 kb)
Supplementary fig. 1

Effects of Carvedilol on the cell viability of N2a/Swe.D9 cells. N2a/Swe.D9 was treated with Carvedilol at the concentrations of 2 nm, 20 nM, 200 nM, 2 μM, 20 μM, 200 μM, and 2 mM for 24 h. Cell viability was determined by the MTT assay (*, P < 0.01; **, P < 0.0001 vs. untreatment group). (GIF 114 kb)

12192_2018_881_MOESM1_ESM.tif (59 kb)
High resolution image (TIFF 58 kb)
12192_2018_881_Fig7_ESM.gif (86 kb)
Supplementary fig. 2

Comparison of cell viability of N2a/Wt and N2a/Swe.D9 cells. Equal amount of cells (1 × 105) were plated in each well of 6-well plates. Cell viability was determined after 24 h and 48 h incubation by the MTT assay (*, P < 0.01 vs. N2a/Wt cells). (GIF 86 kb)

12192_2018_881_MOESM2_ESM.tif (51 kb)
High resolution image (TIFF 51 kb)


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Copyright information

© Cell Stress Society International 2018

Authors and Affiliations

  1. 1.Department of NeurologyLiaocheng People’s HospitalLiaochengChina

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