In SH-SY5Y cells, Japanese encephalitis virus activated calpain to cleave BAX into p18 BAX, which moved to mitochondria and triggered cytochrome c, caspase-3, PARP cleavage, and apoptosis. The calpain inhibitor calpeptin attenuated these signals and improved cell viability.
Key findings
- JEV increased calpain and p18 BAX followed by mitochondrial apoptosis. Calpain inhibition reduced each measured step from BAX cleavage through caspase/PARP and cell death. The sequence is mechanistically coherent, but calpain has other substrates and specificity remains incomplete.
Why this matters globally
JEV remains an important cause of encephalitis in Asia with limited specific therapy. Understanding neuronal injury may enable host-directed adjuncts, but antiviral control, immune balance, brain delivery, and safety all matter.
Thai researcher contribution
Mahidol University, Ramathibodi Hospital, and Chulabhorn Graduate Institute combined virology, pathology, toxicology, and biomedical analysis on a disease highly relevant to Asia.
Limitations to consider
A single neuroblastoma cell line was used, without primary neurons, organoids, animals, or patient data. Dose-response, calpeptin toxicity, viral load, and effects on replication are not reported, preventing therapeutic inference.