Evidence mapPaperPMID 42272938Full record

ArticleFrontiers in drug discovery2026

Role of Angiotensin-Converting Enzyme in Cognitive Aging: Evidence from Preclinical and Clinical Studies.

Joshua Smith, Prakashkumar Dobariya, Tanvi R Kadam, Swati S More

Abstract read
In one paragraph

Article in Frontiers in drug discovery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Joshua SmithCenter for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis MN 55455, USA.
Prakashkumar DobariyaCenter for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis MN 55455, USA.
Tanvi R KadamCenter for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis MN 55455, USA.
Swati S MoreCenter for Drug Design, College of Pharmacy, University of Minnesota, Minneapolis MN 55455, USA.

Funding

Identification of small molecules that regulate endogenous opioid signaling by inhibiting angiotensin converting enzymeR01DA056331 · UNIVERSITY OF MINNESOTA · 2025 to 2025
$562k
Domain-specific inhibition of angiotensin-converting enzyme as a therapeutic strategy for opioid use disordersR01DA056675 · UNIVERSITY OF MINNESOTA · 2025 to 2025
$532k
NIDA NIH HHS R01 DA056331NIDA NIH HHS R01 DA056675
6 · The paper itself

Abstract

Angiotensin-Converting Enzyme (ACE, EC 3.4.15.1), also termed as kininase II or dipeptidyl carboxypeptidase I, is a crucial component of the Renin angiotensin system (RAS). ACE is extensively recognized for its role in the regulation of the cardiovascular system. Emerging evidence supports a neurobiological role of ACE, promoting investigations into its central functions responsible for the modulation of memory and cognitive function, particularly through the use of clinically approved ACE inhibitors (ACE-Is). This review comprehensively analyzes preclinical and clinical findings to date to evaluate the contribution of ACE to cognitive processes and discusses its potential as a therapeutic target for cognitive improvement. Mechanistically, ACE influences cognition through regulation of angiotensin II (Ang II) signaling, as well as modulating other neuropeptides such as substance P. These pathways intersect with processes implicated in cognitive decline, including oxidative stress, neuroinflammation, and cholinergic neurotransmission. Pre-clinical studies consistently demonstrate that ACE-Is confer neuroprotective effects by attenuating Ang II-mediated signaling, restoring redox and inflammatory balance, and improving synaptic plasticity. Clinical evidence provides partial support to these findings, although results remain heterogeneous. Variability in clinical outcomes appears to depend on factors such as patient age, baseline comorbidities, and central availability of the ACE-I. Collectively, this study highlights a non-canonical role of central ACE inhibition in modulating cognitive function, suggesting its promise as a therapeutic strategy for addressing age and disease-associated cognitive dysfunction. Future research should thus prioritize delineation of tissue-specific actions of ACE along with comprehensive examination of ACE genotype-drug interactions, and head- to-head comparison of centrally active ACE-Is with other RAS modulators for their nootropic potential.

Indexed as

acetylcholineangiotensin converting enzymeangiotensin IIcognitionneuroinflammationoxidative stresspreclinical and clinical studies

Identifiers

PMID42272938
PMCPMC13249463

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.