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Bard1-Mediated Regulation of Hnrnpa2b1 Ubiquitination and Protein Stability Contributes to Neuronal Ferroptosis and Cognitive Dysfunction Following Ischemic Stroke.

Overview

Authors: Tuming Li1,2, Tianyi Rong2, Zuoting Shen2, Zhenyu Wei2, Deyan Chen2, Ping Zhong2, Li Cao1,3,4,5,6
ORCID iDs: Ping Zhong, Li Cao
  1. Department of Neurology, Suzhou Hospital of Anhui Medical University, Suzhou Municipal Hospital of Anhui Province, Suzhou, Anhui, People's Republic of China
  2. Department of Neurology, Shidong Hospital, Shanghai, People's Republic of China
  3. Department of Neurology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
  4. Department of Genetics and Rare Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
  5. Shanghai Neurological Rare Disease Biobank and Precision Diagnostic Technical Service Platform, Shanghai, People's Republic of China
  6. Neurological Disorder Center, Haikou Orthopedic and Diabetes Hospital of Shanghai Sixth People's Hospital, Haikou, People's Republic of China
Journal: CNS neuroscience & therapeutics, volume 32, issue 8, article e71074
Dates: received 30 March 2026; accepted 28 July 2026; published online 10 August 2026; in print August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1002/cns.71074 · PMID 42573281 · PMCID PMC13455534 · OpenAlex W7202076848
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: behavior only (modality), mouse (organism), Alzheimer's / dementia (population), stroke (population), cellular / molecular (subfield)
Methods: Statistics
Keywords: Bard1, Ferroptosis, Hnrnpa2b1, post‐stroke cognitive impairment, Sptbn2
MeSH: Cognitive Dysfunction*, Ferroptosis*, Heterogeneous-Nuclear Ribonucleoprotein Group A-B*, Ischemic Stroke*, Neurons*, Tumor Suppressor Proteins*, Ubiquitin-Protein Ligases*, Animals, Male, Mice, Mice, Inbred C57BL, Seven in Absentia Proteins, Ubiquitination (* major topic)
Topic: Ferroptosis and cancer prognosis (Pulmonary and Respiratory Medicine, Medicine), according to OpenAlex
Funding: Program for Outstanding Medical Academic Leader of Shanghai (2022LJ011); National Natural Science Foundation of China (82371255); Shanghai Leading Talent Program of Eastern Talent Plan (LJ2025105); Shanghai Science and Technology Innovation Action Plan (23DZ2291500); Yangpu District Science and Technology Commission and Yangpu District Health Commission Specialized Research Project on Traditional Chinese Medicine (YPZYM202311); Program for Shanghai Outstanding Academic Leaders (23XD1402500)
Citations: not cited yet (Europe PMC); 40 references in the paper

Abstract

Aims: N6‐methyladenosine (m6A) facilitates functional recovery following ischemic stroke (IS). This study investigated the role of Sptbn2 in post‐stroke cognitive impairment (PSCI) and the mechanisms regarding m6A.

Methods: HT‐22 cell damage and ferroptosis were analyzed following OGD exposure. pMCAO surgery was performed to establish an IS mouse model. We assessed neurological deficits and cognitive impairment in mice using the mNSS, adhesive removal test, rotarod test, novel object recognition test, and Y‐maze test. Adeno‐associated viral vectors with overexpression of Sptbn2 combined with pMCAO surgery were used to analyze cognitive dysfunction and ferroptosis.

Results: Sptbn2 was reduced in neurons of PSCI mice. Sptbn2 overexpression alleviated ferroptosis‐induced neuronal damage by promoting the membrane translocation of Slc7a11. Hnrnpa2b1 promoted Sptbn2 stability through an m6A‐related mechanism. Knockdown of Sptbn2 reversed the mitigation of ferroptosis by Hnrnpa2b1 and exacerbated the neuronal injury. Under OGD, Bard1 knockdown reduced the Hnrnpa2b1 ubiquitination, slowed Hnrnpa2b1 degradation, and restored Sptbn2 expression. Knockdown of Bard1 alleviated neuronal ferroptosis, thereby reducing the development of cognitive impairment in mice, a phenotype reversed by Hnrnpa2b1 or Sptbn2 knockdown.

Conclusion: In IS, Bard1‐associated regulation of Hnrnpa2b1 ubiquitination is accompanied by reduced Sptbn2 expression and impaired Slc7a11 membrane translocation, and is involved in neuronal ferroptosis‐related damage.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 5 keywords, 13 MeSH terms, 6 funders, 40 references.

Cite

This paper

Li, T., Rong, T., Shen, Z., Wei, Z., Chen, D., Zhong, P., & Cao, L. (2026). Bard1-Mediated Regulation of Hnrnpa2b1 Ubiquitination and Protein Stability Contributes to Neuronal Ferroptosis and Cognitive Dysfunction Following Ischemic Stroke. CNS neuroscience & therapeutics, 32(8), e71074. https://doi.org/10.1002/cns.71074

BibTeX

@article{li2026bard1,
author = {Li, Tuming and Rong, Tianyi and Shen, Zuoting and Wei, Zhenyu and Chen, Deyan and Zhong, Ping and Cao, Li},
title = {{Bard1-Mediated Regulation of Hnrnpa2b1 Ubiquitination and Protein Stability Contributes to Neuronal Ferroptosis and Cognitive Dysfunction Following Ischemic Stroke}},
journal = {CNS neuroscience \& therapeutics},
year = {2026},
month = aug,
volume = {32},
number = {8},
pages = {e71074},
publisher = {Wiley},
issn = {1755-5930},
doi = {10.1002/cns.71074},
url = {https://doi.org/10.1002/cns.71074},
pmid = {42573281},
pmcid = {PMC13455534}
}

RIS

TY - JOUR
AU - Li, Tuming
AU - Rong, Tianyi
AU - Shen, Zuoting
AU - Wei, Zhenyu
AU - Chen, Deyan
AU - Zhong, Ping
AU - Cao, Li
TI - Bard1-Mediated Regulation of Hnrnpa2b1 Ubiquitination and Protein Stability Contributes to Neuronal Ferroptosis and Cognitive Dysfunction Following Ischemic Stroke
T2 - CNS neuroscience & therapeutics
J2 - CNS Neurosci Ther
PY - 2026
DA - 2026/08/01
VL - 32
IS - 8
SP - e71074
SN - 1755-5930
PB - Wiley
DO - 10.1002/cns.71074
UR - https://doi.org/10.1002/cns.71074
LA - en
ER -

CSL-JSON

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