Evidence map›Paper›PMID 39048074›Full record

ArticleJournal of advanced research2024

CRISPR/Cas9-mediated neuronal deletion of 5-lipoxygenase alleviates deficits in mouse models of epilepsy.

Qiwen Guan, Zhaojun Wang, Kai Zhang, Zhaoqian Liu, Honghao Zhou, Danfeng Cao, Xiaoyuan Mao

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
  2. CRISPR-Based Gene Therapy for Brain Disease.Molecular neurobiology · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Genetic medicines for epilepsy: unlocking new avenues for seizure control.Frontiers in bioengineering and biotechnology · 2026
    Review
  7. 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

7 authors.

Qiwen GuanDepartment of Clinical Pharmacology and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology and Engineering Research Center of Applied Technology of Pharmacogenomics of Ministry of Education, Central South University, Changsha 410078, China; Department of Clinical Pharmacy, Jiaozuo People's Hospital, Jiaozuo 454000, China.
Zhaojun WangDepartment of Clinical Pharmacology and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology and Engineering Research Center of Applied Technology of Pharmacogenomics of Ministry of Education, Central South University, Changsha 410078, China.
Kai ZhangDepartment of Clinical Pharmacology and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology and Engineering Research Center of Applied Technology of Pharmacogenomics of Ministry of Education, Central South University, Changsha 410078, China.
Zhaoqian LiuDepartment of Clinical Pharmacology and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology and Engineering Research Center of Applied Technology of Pharmacogenomics of Ministry of Education, Central South University, Changsha 410078, China.
Honghao ZhouDepartment of Clinical Pharmacology and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology and Engineering Research Center of Applied Technology of Pharmacogenomics of Ministry of Education, Central South University, Changsha 410078, China.
Danfeng CaoAcademician Workstation and Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid, Changsha Medical University, Changsha 410219, China.
Xiaoyuan MaoDepartment of Clinical Pharmacology and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Clinical Pharmacology and Engineering Research Center of Applied Technology of Pharmacogenomics of Ministry of Education, Central South University, Changsha 410078, China. Electronic address: xiaoyuanm@csu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionOur previous work reveals a critical role of activation of neuronal Alox5 in exacerbating brain injury post seizures. However, whether neuronal Alox5 impacts the pathological process of epilepsy remains unknown.

objectivesTo prove the feasibility of neuron-specific deletion of Alox5 via CRISPR-Cas9 in the blockade of seizure onset and epileptic progression.

methodsHere, we employed a Clustered regularly interspaced short-palindromic repeat-associated proteins 9 system (CRISPR/Cas9) system delivered by adeno-associated virus (AAV) to specifically delete neuronal Alox5 gene in the hippocampus to explore its therapeutic potential in various epilepsy mouse models and possible mechanisms.

resultsNeuronal depletion of Alox5 was successfully achieved in the brain. AAV delivery of single guide RNA of Alox5 in hippocampus resulted in reducing seizure severity, delaying epileptic progression and improving epilepsy-associated neuropsychiatric comorbidities especially anxiety, cognitive deficit and autistic-like behaviors in pilocarpine- and kainic acid-induced temporal lobe epilepsy (TLE) models. In addition, neuronal Alox5 deletion also reversed neuron loss, neurodegeneration, astrogliosis and mossy fiber sprouting in TLE model. Moreover, a battery of tests including analysis of routine blood test, hepatic function, renal function, routine urine test and inflammatory factors demonstrated no noticeable toxic effect, suggesting that Alox5 deletion possesses the satisfactory biosafety. Mechanistically, the anti-epileptic effect of Alox5 deletion might be associated with reduction of glutamate level to restore excitatory/inhibitory balance by reducing CAMKII-mediated phosphorylation of Syn I

conclusionOur findings showed the translational potential of AAV-mediated delivery of CRISPR-Cas9 system including neuronal Alox5 gene for an alternative promising therapeutic approach to treat epilepsy.

Indexed as

Arachidonate 5-LipoxygenaseCRISPR-Cas SystemsDisease Models, AnimalEpilepsyHippocampusNeuronsAnimalsDependovirusEpilepsy, Temporal LobeGene DeletionMaleMiceMice, Inbred C57BLPilocarpineArachidonate 5-LipoxygenasePilocarpineAlox5Cas9CRISPREpilepsyGene therapy

Identifiers

PMID39048074
PMCPMC11379977

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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.