Evidence map›Paper›PMID 41983942›Full record

ReviewExperimental physiology2026

Neuroprotective roles of klotho: Molecular pathways and therapeutic implications for cognitive health in neurological and psychiatric diseases.

Amir Arsalan Ghahari, Leylinaz Safaeihavadaragh, Mehrdad Nourizadeh, Shaghayegh Davari, Saba Safaei, Farshad Zare, Safa Alkayyat, Erfan Kamali Far

Abstract readReview
In one paragraph

Review in Experimental physiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
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.

Amir Arsalan GhahariNeurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.ORCID https://orcid.org/0009-0005-6476-5998
Leylinaz SafaeihavadaraghSemmelweis University, Budapest, Hungary.ORCID https://orcid.org/0009-0008-6917-518X
Mehrdad NourizadehNeurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.ORCID https://orcid.org/0009-0009-1347-9149
Shaghayegh DavariNeurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.ORCID https://orcid.org/0009-0007-3242-2688
Saba SafaeiSchool of Medicine, Arak University of Medical Sciences, Arak, Iran.ORCID https://orcid.org/0009-0000-0719-5881
Farshad ZareStudent Research Committee, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
Safa AlkayyatDepartment of Medical Analysis, Medical Laboratory Technique College, The Islamic University, Najaf, Iraq.
Erfan Kamali FarNeurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.ORCID https://orcid.org/0009-0006-2199-8940

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Klotho, a pleiotropic protein initially identified for its role in kidney function, has garnered significant attention for its neuroprotective properties in various neurodegenerative diseases. It regulates key processes, such as oxidative stress, neuroinflammation, synaptic plasticity and myelination, all crucial for maintaining neuronal integrity and cognitive function. Preclinical studies demonstrate that klotho enhances amyloid-β and tau clearance, stabilizes synaptic function, supports oligodendrocyte maturation and mitigates excitotoxicity. Clinical findings show that higher α-klotho levels are associated with slower cognitive decline in Alzheimer's and Parkinson's diseases, improved outcomes in multiple sclerosis and better recovery after stroke. Notably, the protective effects of klotho appear most pronounced in individuals with high genetic or pathological risks, such as apolipoprotein E ε4 carriers in Alzheimer's disease. Despite these promising insights, the clinical application of klotho-based therapies is hindered by variability in biomarker assays, challenges in crossing the blood-brain barrier, and the need for precision-based interventions tailored to individual genetic profiles. Current strategies to enhance klotho activity include lifestyle changes, pharmacological agents, recombinant protein delivery and gene therapy. Although challenges remain, klotho stands as a potential therapeutic target for mitigating cognitive decline and promoting brain health across a range of neurodegenerative and cerebrovascular conditions.

Indexed as

CognitionGlucuronidaseKlotho ProteinsMental DisordersNervous System DiseasesNeurodegenerative DiseasesNeuroprotectionNeuroprotective AgentsAnimalsHumansNeuronal PlasticityGlucuronidaseKlotho ProteinsNeuroprotective AgentsAlzheimer's diseasecognitive declineklothoneuroprotectionpharmacological interventionsynaptic plasticity

Identifiers

PMID41983942
PMCPMC13327344

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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.