Evidence map›Paper›PMID 41298976›Full record

ReviewInflammopharmacology2026

Pharmacological modulation of the PI3K/AKT/GSK3β axis: a new frontier in Alzheimer's disease treatment.

Saad Misfer Alqahtani, Hayder M Al-Kuraishy, Ali I Al-Gareeb, Ali K Albuhadily, Mustafa M Shokr, Athanasios Alexiou, Marios Papadakis, Gaber El-Saber Batiha

Abstract readReview
PubMed Publisher
In one paragraph

Review in Inflammopharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Article
  2. Intranasal Administration of Isoeugenol Improves Memory Deficits in APP/PS1 Old Mice-A Role Beyond Nrf2 Activation?FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
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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

8 authors.

Saad Misfer AlqahtaniDepartment of Pathology, College of Medicine, The University Hospital, 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 Jabir Ibn Hayyan Medical University, Al-Ameer Qu, Najaf, Iraq.
Ali K AlbuhadilyDepartment of Clinical Pharmacology and Medicine, College of Medicine, Mustansiriyah University, Baghdad, Iraq.
Mustafa M ShokrDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Sinai University-Arish Branch, Arish, 45511, Egypt. mostafa.mohsen@su.edu.eg.ORCID http://orcid.org/0000-0001-5221-4666
Athanasios AlexiouUniversity Centre for Research and Development, Chandigarh University, Mohali, India.
Marios PapadakisDepartment of Surgery II, University Hospital Witten-Herdecke, University of Witten-Herdecke, Heusnerstrasse 40, 42283, Wuppertal, Germany. drmariospapadakis@gmail.com.
Gaber El-Saber BatihaDepartment of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, 22511, AlBeheira, Egypt.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Amyloid-beta (Aβ) plaques and the intracellular buildup of hyperphosphorylated tau protein are hallmarks of Alzheimer's disease (AD), a progressive neurodegenerative disease that causes synaptic dysfunction and neuronal death. Glycogen synthase kinase 3 beta (GSK3β), protein kinase B (AKT), and phosphatidylinositol 3-kinase all have aberrant signaling pathways that contribute to the pathophysiology of AD. The PI3K/AKT neuroprotective pathway is seriously inhibited in AD, which leads to brain insulin resistance (BIR) and neurodegeneration. However, AD leads to hyperactivation of GSK3β, which in turn produces tau hyperphosphorylation, Aβ accumulation, and cognitive impairment. BIR and PI3K/AKT/GSK3β signaling in AD have a complicated interaction that is covered in this article. The pathway has both neuroprotective and pathogenic functions. The therapeutic use of GSK3β inhibitors and PI3K/AKT activators to decrease AD pathogenesis is also discussed. Changing these pathways can improve cognitive function, reduce tau and Aβ pathology, and restore insulin signaling, according to preclinical and clinical research. Finding highly specialized treatments with minimal side effects remains a challenge. More research is required to thoroughly assess the safety and efficacy of medications that target specific pathways and to clarify the molecular mechanisms underlying PI3K/AKT/GSK3β dysregulation in AD in order to create novel and effective treatment alternatives.

Indexed as

Alzheimer DiseaseGlycogen Synthase Kinase 3 betaPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktAmyloid beta-PeptidesAnimalsHumansNeuroprotective AgentsSignal Transductiontau ProteinsAmyloid beta-PeptidesGlycogen Synthase Kinase 3 betaNeuroprotective AgentsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-akttau ProteinsAlzheimer's diseaseAmyloid-betaBrain insulin resistanceGlycogen synthase kinase 3 betaPhosphatidylinositol 3-kinase

Identifiers

PMID41298976

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.