Spike RBD drives sustained Parkinson’s disease progression via microglia-neuron crosstalk-mediated RTP801 upregulation
Our findings demonstrate that SARS-CoV-2 RBD exacerbates PD progression through a pathogenic crosstalk between microglia and neurons. This neurotoxic signaling is mediated by a mitochondrial mtDNA-cGAS-STING-IFNβ/RTP801 axis. Targeting RTP801 or the STING pathway may therefore represent a promising therapeutic strategy to mitigate long COVID-associated progression of PD.
Authors
- Yin Zhao (ORCID: https://orcid.org/0000-0002-1470-7184)
- Shifeng Chu (ORCID: https://orcid.org/0000-0002-6406-9846)
- Kaichao Hu
- Nai‐Hong Chen (ORCID: https://orcid.org/0009-0001-6442-8191)
- Wenbin He (ORCID: https://orcid.org/0000-0002-9372-052X)
- Zhao Zhang (ORCID: https://orcid.org/0000-0001-5363-2157)
- Shasha Wang (ORCID: https://orcid.org/0000-0002-3172-3899)
- Wenfei Wang (ORCID: https://orcid.org/0000-0003-3360-8082)
- Yan Xu (ORCID: https://orcid.org/0009-0001-3964-4343)
- Ruo-Lan Yuan
- Ye Peng
Institutions
- Shanxi University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
Publication Details
- Journal
- Journal of Advanced Research
- Published
- 2025-08-01
- DOI
- https://doi.org/10.1016/j.jare.2025.07.060
- Citations
- 3
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 2.53
Funders
- National Natural Science Foundation of China
- Chinese Academy of Medical Sciences Initiative for Innovative Medicine