Evidence map›Paper›PMID 42268366›Full record

ReviewJournal of molecular neuroscience : MN2026

Unlocking Neuroprotection: Exercise-Induced Muscle Secretome (Myokines) as a Therapeutic Avenue Against Alzheimer's Disease Pathogenesis.

Hossein Shirvani, Linda S Pescatello, Ali Reza Eftekhari Moghadam, Ehsan Arabzadeh

Abstract readReview
PubMed Publisher
In one paragraph

Review in Journal of molecular neuroscience : MN, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Hossein ShirvaniExercise Physiology Research Center, LifeStyle Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.ORCID http://orcid.org/0000-0002-0696-958X
Linda S PescatelloDepartment of Kinesiology, University of Connecticut, Storrs, CT, USA.ORCID http://orcid.org/0000-0002-5841-798X
Ali Reza Eftekhari MoghadamDepartment of Anatomical Science, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran.ORCID http://orcid.org/0000-0001-7680-8653
Ehsan ArabzadehExercise Physiology Research Center, LifeStyle Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran. eh.arabzadeh@gmail.com.ORCID http://orcid.org/0000-0003-2907-9798

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This review critically evaluates exercise-induced myokines as neuroprotective agents against Alzheimer's disease (AD) and is structured around three thematic sections: (1) mechanistic foundations of myokine neuroprotection, (2) translational barriers to therapeutic development, and (3) a strategic framework for future research. Epidemiological studies associate physical exercise with reduced AD risk (30-45%), yet mechanisms remain incompletely resolved. Preclinical studies demonstrate that exercise-induced myokines (Irisin, BDNF, Cathepsin B) modulate AD pathology by: (1) attenuating amyloid-beta (Aβ)/tau accumulation, (2) suppressing neuroinflammation, and (3) enhancing synaptic plasticity. However, human exercise interventions show conflicting results influenced by APOE genotype, age, and exercise modality. Associative human data suggest that Interleukin-6 (IL-6) exemplifies pleiotropy-affording neuroprotective effects in acute contexts but potentially detrimental effects in states of chronic inflammation. Therapeutic hurdles include blood-brain barrier (BBB) penetration, pleiotropic risks, and patient heterogeneity. Emerging concepts such as combinatorial approaches (nanocarriers, exercise mimetics) and biomarker-driven trials are proposed as hypothetical future strategies; however, these remain unvalidated and require substantial preclinical development before implemented in clinical care. This narrative review is structured around three thematic sections: mechanistic foundations of myokine neuroprotection, translational barriers to therapeutic development, and a strategic framework for future research. The muscle-brain axis represents a compelling but complex therapeutic target. Based on current preclinical and correlational human evidence, future research should prioritize mechanistic rigor, standardized biomarker validation, and clinically viable delivery strategies. Notably, several approaches discussed herein-including nanocarrier delivery systems, exercise mimetics, and combinatorial myokine cocktails-remain speculative and are presented as future research directions rather than established therapeutic interventions.

Indexed as

Alzheimer DiseaseExerciseMyokinesNeuroprotective AgentsAnimalsHumansNeuroprotectionMyokinesNeuroprotective AgentsMuscle-brain axisPatient stratificationPreclinical modelsRecombinant proteinsSynaptic plasticity

Identifiers

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.