Int. J. Mol. Sci. 2013, 14(8), 16917-16942; doi:10.3390/ijms140816917
Article

ACE Inhibition with Captopril Retards the Development of Signs of Neurodegeneration in an Animal Model of Alzheimer’s Disease

1 Molecular Pharmacology Unit, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH) Zurich, Zurich CH-8057, Switzerland 2 Institute of Pharmacology and Toxicology, Department of Medicine, University of Zurich, Zurich CH-8057, Switzerland
* Author to whom correspondence should be addressed.
Received: 17 May 2013; in revised form: 31 July 2013 / Accepted: 12 August 2013 / Published: 16 August 2013
(This article belongs to the Special Issue Oxidative Stress and Ageing)
PDF Full-text Download PDF Full-Text [7506 KB, uploaded 16 August 2013 13:06 CEST]
Abstract: Increased generation of reactive oxygen species (ROS) is a significant pathological feature in the brains of patients with Alzheimer’s disease (AD). Experimental evidence indicates that inhibition of brain ROS could be beneficial in slowing the neurodegenerative process triggered by amyloid-beta (Abeta) aggregates. The angiotensin II AT1 receptor is a significant source of brain ROS, and AD patients have an increased brain angiotensin-converting enzyme (ACE) level, which could account for an excessive angiotensin-dependent AT1-induced ROS generation. Therefore, we analyzed the impact of ACE inhibition on signs of neurodegeneration of aged Tg2576 mice as a transgenic animal model of AD. Whole genome microarray gene expression profiling and biochemical analyses demonstrated that the centrally active ACE inhibitor captopril normalized the excessive hippocampal ACE activity of AD mice. Concomitantly, the development of signs of neurodegeneration was retarded by six months of captopril treatment. The neuroprotective profile triggered by captopril was accompanied by reduced amyloidogenic processing of the amyloid precursor protein (APP), and decreased hippocampal ROS, which is known to enhance Abeta generation by increased activation of beta- and gamma-secretases. Taken together, our data present strong evidence that ACE inhibition with a widely used cardiovascular drug could interfere with Abeta-dependent neurodegeneration.
Keywords: Alzheimer’s disease; amyloid precursor protein; angiotensin-converting enzyme; AT1 receptor; captopril; neurodegeneration; Tg2576 mouse model

Supplementary Files

Article Statistics

Load and display the download statistics.

Citations to this Article

Cite This Article

MDPI and ACS Style

AbdAlla, S.; Langer, A.; Fu, X.; Quitterer, U. ACE Inhibition with Captopril Retards the Development of Signs of Neurodegeneration in an Animal Model of Alzheimer’s Disease. Int. J. Mol. Sci. 2013, 14, 16917-16942.

AMA Style

AbdAlla S, Langer A, Fu X, Quitterer U. ACE Inhibition with Captopril Retards the Development of Signs of Neurodegeneration in an Animal Model of Alzheimer’s Disease. International Journal of Molecular Sciences. 2013; 14(8):16917-16942.

Chicago/Turabian Style

AbdAlla, Said; Langer, Andreas; Fu, Xuebin; Quitterer, Ursula. 2013. "ACE Inhibition with Captopril Retards the Development of Signs of Neurodegeneration in an Animal Model of Alzheimer’s Disease." Int. J. Mol. Sci. 14, no. 8: 16917-16942.

Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert