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Cited by 100Alzheimer's disease research and treatmentsCholinesterase and Neurodegenerative DiseasesRenin-Angiotensin System Studies

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

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AbdAlla, Said, Langer, Andreas, Fu, Xuebin, Quitterer, Ursula·2013·International Journal of Molecular Sciences
DOI 10.3390/ijms140816917PMC PMC3759943
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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.

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Authors
AbdAlla, S., Langer, A., Fu, X., & Quitterer, U.
Affiliations
  • ETH Zurich (CH)
  • University of Zurich (CH)
Corresponding author
Quitterer, Ursula
ORCID
Fu, Xuebin
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2013-08-16
Volume
14
Issue
8
Pages
16917-16942
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms140816917
PMC
PMC3759943
OpenAlex
W2003923036
Cited by
100
References
6
Citations by year
2026: 5 · 2025: 8 · 2024: 4 · 2023: 12 · 2022: 10 · 2021: 13 · 2020: 8 · 2019: 7 · 2018: 6 · 2017: 7 · 2016: 11 · 2015: 4 · 2014: 4 · 2012: 1
FWCI
3.93
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Repository for Publications and Research Data (ETH Zurich) (submittedVersion, cc-by)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
  • ETH Zürich Research Collection (cc-by)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
  • National Science Foundation
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (140679)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Keywords
captopril, angiotensin-converting enzyme inhibition, Alzheimer's disease, neurodegeneration, reactive oxygen species, angiotensin II type 1 receptor, amyloid-beta, APP processing, beta-secretase, gamma-secretase, hippocampus, Tg2576 mice, neuroprotection, gene expression profiling
MeSH terms
Alzheimer Disease, Angiotensin II, Angiotensin-Converting Enzyme Inhibitors, Animals, Captopril, Disease Models, Animal, Hippocampus, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Regeneration, Oxidation-Reduction, Up-Regulation, Amyloid beta-Peptides, Reactive Oxygen Species, Oligonucleotide Array Sequence Analysis, Protein Transport, Receptor, Angiotensin, Type 1, Mice, Plaque, Amyloid, Transcriptome

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