Bard1-Mediated Regulation of Hnrnpa2b1 Ubiquitination and Protein Stability Contributes to Neuronal Ferroptosis and Cognitive Dysfunction Following Ischemic Stroke.
Overview
- Department of Neurology, Suzhou Hospital of Anhui Medical University, Suzhou Municipal Hospital of Anhui Province, Suzhou, Anhui, People's Republic of China
- Department of Neurology, Shidong Hospital, Shanghai, People's Republic of China
- Department of Neurology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China
- 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
- Shanghai Neurological Rare Disease Biobank and Precision Diagnostic Technical Service Platform, Shanghai, People's Republic of China
- Neurological Disorder Center, Haikou Orthopedic and Diabetes Hospital of Shanghai Sixth People's Hospital, Haikou, People's Republic of China
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.
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Data
Datasets cited
- geo:GSE178997, at NCBI GEO; found in the text, “Sptbn2 Overexpression in Hippocampal Neurons…”
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
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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://
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/
url = {https://
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/
VL - 32
IS - 8
SP - e71074
SN - 1755-5930
PB - Wiley
DO - 10.1002/
UR - https://
LA - en
ER -
CSL-JSON
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