Evidence mapPaperPMID 37847125Full record

ReviewJournal of cellular and molecular medicine2024

Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective.

Naif H Ali, Hayder M Al-Kuraishy, Ali I Al-Gareeb, Saud A Alnaaim, Athanasios Alexiou, Marios Papadakis, Asmaa A Khalifa, Hebatallah M Saad, Gaber El-Saber Batiha

Erratum issuedOpen access · goldAbstract readReview
In one paragraph

Review in Journal of cellular and molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
7.0field-weighted citation impact, top 2% of its field
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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.

  1. Pooled it
  2. Arsenic Promotes Intracellular AβBiological trace element research · 2026
    Article
  3. Review
  4. PARP1 deficiency mitigates amyloid pathology, neurodegeneration, and cognitive decline in a familial Alzheimer's disease model.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy.Journal of cellular and molecular medicine · 2024
    Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 7 institutions in 4 countries.

Naif H AliDepartment of Internal Medicine, Medical College, Najran University, Najran, Saudi Arabia.
Hayder M Al-KuraishyDepartment of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq.
Ali I Al-GareebDepartment of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq.
Saud A AlnaaimClinical Neurosciences Department, College of Medicine, King Faisal University, Hofuf, Saudi Arabia.
Athanasios AlexiouDepartment of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, New South Wales, Australia.ORCID 0000-0002-2206-7236
Marios PapadakisDepartment of Surgery II, University Hospital Witten-Herdecke, University of Witten-Herdecke, Wuppertal, Germany.
Asmaa A KhalifaDepartment of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt.
Hebatallah M SaadDepartment of Pathology, Faculty of Veterinary Medicine, Matrouh University, Matrouh, Egypt.ORCID 0000-0001-9555-7300
Gaber El-Saber BatihaDepartment of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, AlBeheira, Egypt.
Mustansiriyah University · IQDamanhour University · EGEgypt Nanotechnology Center · EGKing Faisal University · SANajran University · SAPharos University in Alexandria · EGWitten/Herdecke University · DE

Funding

University of Witten-Herdecke Germany
6 · The paper itself

Abstract

Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease with multifaceted neuropathological disorders. AD is characterized by intracellular accumulation of phosphorylated tau proteins and extracellular deposition of amyloid beta (Aβ). Various protease enzymes, including neprilysin (NEP), are concerned with the degradation and clearance of Aβ. Indeed, a defective neuronal clearance pathway due to the dysfunction of degradation enzymes might be a possible mechanism for the accumulation of Aβ and subsequent progression of AD neuropathology. NEP is one of the most imperative metalloproteinase enzymes involved in the clearance of Aβ. This review aimed to highlight the possible role of NEP inhibitors in AD. The combination of sacubitril and valsartan which is called angiotensin receptor blocker and NEP inhibitor (ARNI) may produce beneficial and deleterious effects on AD neuropathology. NEP inhibitors might increase the risk of AD by the inhibition of Aβ clearance, and increase brain bradykinin (BK) and natriuretic peptides (NPs), which augment the pathogenesis of AD. These verdicts come from animal model studies, though they may not be applied to humans. However, clinical studies revealed promising safety findings regarding the use of ARNI. Moreover, NEP inhibition increases various neuroprotective peptides involved in inflammation, glucose homeostasis and nerve conduction. Also, NEP inhibitors may inhibit dipeptidyl peptidase 4 (DPP4) expression, ameliorating insulin and glucagon-like peptide 1 (GLP-1) levels. These findings proposed that NEP inhibitors may have a protective effect against AD development by increasing GLP-1, neuropeptide Y (NPY) and substance P, and deleterious effects by increasing brain BK. Preclinical and clinical studies are recommended in this regard.

Indexed as

Alzheimer DiseaseNeurodegenerative DiseasesAmyloid beta-PeptidesAnimalsGlucagon-Like Peptide 1HumansNeprilysinAmyloid beta-PeptidesGlucagon-Like Peptide 1NeprilysinAlzheimer's diseaseneprilysinneprilysin inhibitors

Identifiers

PMID37847125
PMCPMC10826440
OpenAlexW4387692654

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.