Therapeutic Effect of Rapamycin on TDP-43-Related Pathogenesis in Ischemic Stroke

Yi Syue Tsou, Jing Huei Lai, Kai Yun Chen, Cheng Fu Chang, Chi Chen Huang

Research output: Contribution to journalArticlepeer-review


Stroke is a major cause of death and disability across the world, and its detrimental impact should not be underestimated. Therapies are available and effective for ischemic stroke (e.g., thrombolytic recanalization and mechanical thrombectomy); however, there are limitations to therapeutic interventions. Recanalization therapy has developed dramatically, while the use of adjunct neuroprotective agents as complementary therapies remains deficient. Pathological TAR DNA-binding protein (TDP-43) has been identified as a major component of insoluble aggregates in numerous neurodegenerative pathologies, including ALS, FTLD and Alzheimer’s disease. Here, we show that increased pathological TDP-43 fractions accompanied by impaired mitochondrial function and increased gliosis were observed in an ischemic stroke rat model, suggesting a pathological role of TDP-43 in ischemic stroke. In ischemic rats administered rapamycin, the insoluble TDP-43 fraction was significantly decreased in the ischemic cortex region, accompanied by a recovery of mitochondrial function, the attenuation of cellular apoptosis, a reduction in infarct areas and improvements in motor defects. Accordingly, our results suggest that rapamycin provides neuroprotective benefits not only by ameliorating pathological TDP-43 levels, but also by reversing mitochondrial function and attenuating cell apoptosis in ischemic stroke.

Original languageEnglish
Article number676
JournalInternational journal of molecular sciences
Issue number1
Publication statusPublished - Jan 2023


  • ischemic stroke
  • rapamycin
  • TDP-43

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


Dive into the research topics of 'Therapeutic Effect of Rapamycin on TDP-43-Related Pathogenesis in Ischemic Stroke'. Together they form a unique fingerprint.

Cite this