TAB2 Causes Neuronal Damage by Aggravating Microglia-Mediated Neuroinflammation in Parkinson's Disease.
Overview
- Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Department of Neurosurgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
Abstract
Neuroinflammation plays a key role in exacerbating dopaminergic neuron loss in Parkinson's disease (PD). We identified TAB2 as an early‐stage biomarker, which was elevated in PD patients’ microglia. However, the role of TAB2 in the pathogenesis of PD remains unknown. In this study, we found that Tab2 knockdown inhibited the activation of microglia and protected neurons in PD models. STAT3, as a transcription factor for TAB2, regulated TAB2 expression. Mechanistically, TAB2 interacted with α‐synuclein and facilitated the recognition of K63‐linked ubiquitin chains, leading to the formation of the TAK1–TABs complex and activation of TAK1, which was ultimately followed by activation of the nuclear factor‐kappa B (NF‐κB) signaling pathway. Furthermore, microglia‐specific knockdown of Tab2 significantly inhibited microglia activation, protected dopaminergic neurons, improved motor function, and attenuated anxiety‐like behaviors in PD mouse model. We further showed that the FDA‐approved drug, lumacaftor, suppressed microglial TAB2 expression and had potent anti‐inflammatory and neuroprotective effects in PD models. Taken together, our study reveals that the STAT3–TAB2–NF‐κB–IL‐1β positive feedback axis in microglia is a crucial checkpoint that exacerbates neuroinflammation in PD. Therefore, these findings identify a pivotal role of TAB2 in regulating microglia‐mediated neuroinflammation, suggesting that targeting TAB2 may be a possible therapeutic strategy for PD.
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data
Datasets cited
- geo:GSE157783 — at NCBI GEO; found in the text, “The snRNA‐Seq Data Processing”
Data Availability Statement
The data that support the findings of this study are openly available in ModelArchive at https://
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, pages, dates, 13 authors, 4 keywords, 4 funders, 56 references.
Cite
This paper
Zhao, Y., Huang, Z., Gao, J., Li, A., Wang, H., Chen, Y., Zhu, G., Zhang, X., Jiang, Y., Zhang, M., Meng, F., Zhang, J., & Du, T. (2026). TAB2 Causes Neuronal Damage by Aggravating Microglia-Mediated Neuroinflammation in Parkinson's Disease. Advanced science (Weinheim, Baden-Wurttemberg, Germany), e77175. https://
BibTeX
@article{zhao2026tab2,
author = {Zhao, Yanhao and Huang, Zimeng and Gao, Jianing and Li, Aolan and Wang, Huizhi and Chen, Yingchuan and Zhu, Guanyu and Zhang, Xin and Jiang, Yin and Zhang, Moxuan and Meng, Fangang and Zhang, Jianguo and Du, Tingting},
title = {{TAB2 Causes Neuronal Damage by Aggravating Microglia-Mediated Neuroinflammation in Parkinson's Disease}},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = aug,
pages = {e77175},
publisher = {Wiley},
issn = {2198-3844},
doi = {10.1002/
url = {https://
pmid = {42606072},
pmcid = {PMC13479592}
}
RIS
TY - JOUR
AU - Zhao, Yanhao
AU - Huang, Zimeng
AU - Gao, Jianing
AU - Li, Aolan
AU - Wang, Huizhi
AU - Chen, Yingchuan
AU - Zhu, Guanyu
AU - Zhang, Xin
AU - Jiang, Yin
AU - Zhang, Moxuan
AU - Meng, Fangang
AU - Zhang, Jianguo
AU - Du, Tingting
TI - TAB2 Causes Neuronal Damage by Aggravating Microglia-Mediated Neuroinflammation in Parkinson's Disease
T2 - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
J2 - Adv Sci (Weinh)
PY - 2026
DA - 2026/
SP - e77175
SN - 2198-3844
PB - Wiley
DO - 10.1002/
UR - https://
LA - en
ER -
CSL-JSON
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