Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 3 complete abstracts (591 words), 9 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Agents, Neuroprotective; Neuroprotectant; Neuroprotectants; Neuroprotective Agent; Agent, Neuroprotective; Neuroprotective Drug; Drug, Neuroprotective; Neuroprotective Drugs.
Where it fits in the MeSH classification
- Broader topics
- Protective Agents; Central Nervous System Agents
Research landscape
PubMed indexes 50,475 records tagged with the MeSH heading “Neuroprotective Agents” (counts retrieved 2026-10-29). 15,014 of them (29.7%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 20,750 records.
Reviews account for 8,924 records (17.7%) and meta-analyses for 255. Randomized controlled trials number 968 (1.9%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 2,156 |
| 2000-2009 | 12,555 |
| 2010-2019 | 20,750 |
| 2020 onward | 15,014 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 8,924 | 17.7% |
| Meta-analyses | 255 | 0.5% |
| Randomized controlled trials | 968 | 1.9% |
Method: PubMed query "Neuroprotective Agents"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in pharmacology
Drug evidence builds in layers: laboratory pharmacology describes how a compound acts, pharmacokinetic studies describe how the body handles it, and randomized trials test whether it helps and what harms it causes. Post-marketing surveillance and observational studies reveal rarer adverse effects but cannot prove causation. This page is educational and is not a recommendation to start, stop or change any medicine; decisions about treatment belong with a qualified clinician.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| SIRT1 Activators as Geroprotective Agents in Brain Aging: Mechanisms and Therapeutic Potential | 2026 | Review article Design not recorded in structured metadata | 3 | cc by PMID 41934491 · DOI · PMC13050347 |
| The exercise hormone irisin has neuroprotective effects in a mouse model of multiple sclerosis | 2026 | Research article Design not recorded in structured metadata | 2 | cc by PMID 42168599 · DOI · PMC13218937 |
| Neuroprotective roles of klotho: Molecular pathways and therapeutic implications for cognitive health in neurological and psychiatric diseases | 2026 | Review article Design not recorded in structured metadata | 2 | cc by PMID 41983942 · DOI · PMC13327344 |
SIRT1 Activators as Geroprotective Agents in Brain Aging: Mechanisms and Therapeutic Potential [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The brain undergoes profound molecular and structural changes during the aging process, resulting in the development of neurodegeneration, cognitive impairment, and increased vulnerability to chronic diseases.
- Closing excerpt
- Thus, SIRT1 could be a promising pharmacological target for age-associated brain disorders, warranting more robust translational studies to validate these findings in humans.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (245 words)
The brain undergoes profound molecular and structural changes during the aging process, resulting in the development of neurodegeneration, cognitive impairment, and increased vulnerability to chronic diseases. At the cellular level, brain aging is characterized by oxidative damage, genomic instability, and chronic low-grade inflammation known as inflammaging. Central to this process is Sirtuin 1 (SIRT1), a NAD+-dependent class III histone deacetylase, known for its regulatory role in chromatin remodeling, oxidative stress responses, mitochondrial biogenesis, and neuroplasticity. Recent research has identified SIRT1 as a molecular target capable of reversing or attenuating several hallmarks of aging, particularly within the central nervous system (CNS). This narrative review critically evaluates the emerging evidence surrounding the geroprotective effects of SIRT1 activators, which exert dual actions, senomorphic and senolytic, via modulation of signaling pathways, thereby reducing neuronal senescence, enhancing autophagy, and mitigating inflammatory responses. The discussion also addresses the region-specific role of SIRT1 across the brain, particularly in the hippocampus and hypothalamus, which are essential for memory, energy homeostasis, and resilience to stress. Additionally, this review explores how SIRT1 depletion during aging contributes to the development of synaptic dysfunction, impaired cognitive function, and susceptibility to neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). The therapeutic potential of SIRT1 activators is supported by preclinical and early clinical studies, suggesting their value in preventing or delaying brain aging. Thus, SIRT1 could be a promising pharmacological target for age-associated brain disorders, warranting more robust translational studies to validate these findings in humans.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41934491 · DOI · PMC13050347
The exercise hormone irisin has neuroprotective effects in a mouse model of multiple sclerosis [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Aerobic exercise is a disease-modifying intervention in multiple sclerosis (MS) that ameliorates several progressive neurological symptoms in people with MS.
- Closing excerpt
- Taken together, these findings suggest that irisin induction in response to exercise confers direct neuroprotective effects in an inflammation-driven neurodegenerative condition, making it an attractive therapeutic candidate for MS.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (150 words)
Aerobic exercise is a disease-modifying intervention in multiple sclerosis (MS) that ameliorates several progressive neurological symptoms in people with MS. Here we show that the exercise hormone irisin mediates neuroprotective effects of exercise in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. We demonstrate that voluntary free-wheel running exercise protects against inflammation-induced neurodegeneration in EAE, but these neuroprotective effects are abrogated in mice lacking Fndc5/irisin. Peripheral delivery of irisin increases irisin plasma levels and reduces both clinical symptoms and neuronal loss in EAE. Although peripheral irisin does not alter peripheral and central immune responses in EAE, it induces a direct neuroprotective gene programme in spinal cord neurons and preserves synapses and mitochondrial activity, probably through direct binding to motor neurons. Taken together, these findings suggest that irisin induction in response to exercise confers direct neuroprotective effects in an inflammation-driven neurodegenerative condition, making it an attractive therapeutic candidate for MS.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42168599 · DOI · PMC13218937
Neuroprotective roles of klotho: Molecular pathways and therapeutic implications for cognitive health in neurological and psychiatric diseases [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Klotho, a pleiotropic protein initially identified for its role in kidney function, has garnered significant attention for its neuroprotective properties in various neurodegenerative diseases.
- Closing excerpt
- 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.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (196 words)
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.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41983942 · DOI · PMC13327344
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) [4]
- Research article Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) [5]
- Research article Methylprednisolone for acute spinal cord injury: an inappropriate standard of care [6]
- Research article Pharmacological Management of Lewy Body Dementia: A Systematic Review and Meta-Analysis [7]
- Research article A meta-analysis of the efficacy of donepezil, rivastigmine, galantamine, and memantine in relation to severity of Alzheimer's disease [8]
- Research article Systematic review and meta-analysis of the efficacy of melatonin in experimental stroke [9]
References
- Alameen AAM, Al-Kuraishy HM, Al-Gareeb AI, Alexiou A, Papadakis M, Faheem SA, et al.. SIRT1 Activators as Geroprotective Agents in Brain Aging: Mechanisms and Therapeutic Potential. . 2026. PMID 41934491 · DOI · PMC13050347
- Rosenkranz SC, da Rocha JF, Moreira L, Schlachter P, Bier J, Healy K, et al.. The exercise hormone irisin has neuroprotective effects in a mouse model of multiple sclerosis. . 2026. PMID 42168599 · DOI · PMC13218937
- Ghahari AA, Safaeihavadaragh L, Nourizadeh M, Davari S, Safaei S, Zare F, et al.. Neuroprotective roles of klotho: Molecular pathways and therapeutic implications for cognitive health in neurological and psychiatric diseases. . 2026. PMID 41983942 · DOI · PMC13327344
- Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2012. PMID 22419278 · DOI · PMC7055506
- Miller RG, Mitchell JD, Lyon M, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev. 2007. PMID 17253460 · DOI
- Hurlbert RJ. Methylprednisolone for acute spinal cord injury: an inappropriate standard of care. J Neurosurg. 2000. PMID 10879751 · DOI
- Stinton C, McKeith I, Taylor JP, Lafortune L, Mioshi E, Mak E, et al.. Pharmacological Management of Lewy Body Dementia: A Systematic Review and Meta-Analysis. Am J Psychiatry. 2015. PMID 26085043 · DOI
- Di Santo SG, Prinelli F, Adorni F, Caltagirone C, Musicco M. A meta-analysis of the efficacy of donepezil, rivastigmine, galantamine, and memantine in relation to severity of Alzheimer's disease. J Alzheimers Dis. 2013. PMID 23411693 · DOI
- Macleod MR, O'Collins T, Horky LL, Howells DW, Donnan GA. Systematic review and meta-analysis of the efficacy of melatonin in experimental stroke. J Pineal Res. 2005. PMID 15617535 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.