June 25, 2025 – RNA fragments help neurons resist the damaging effects of Botox (botulinum neurotoxin A, also known as BoNT/A)—the world’s most potent known biological toxin, according to a new study by researchers at the Hebrew University of Jerusalem. 

Published in Genomic Psychiatry, this breakthrough explains how Botox paralyzes muscles without causing neuronal death. This insight could lead to longer-lasting, more precise medical and cosmetic BoNT/A use. 

“We’ve known for years that botulinum toxin paralyzes muscles without destroying the neurons that control them—but we never fully understood why,” explains Hebrew University Professor Hermona Soreq from The Edmond and Lily Safra Center for Brain Sciences (ELSC). “This study shows that the neurons themselves mount an active, RNA-based defense, which could be harnessed to develop more precise and longer-lasting therapeutic applications.” 

The study found that specific transfer RNA fragments—particularly 5′LysTTT tRFs—accumulate in neurons exposed to BoNT/A. These fragments interact with both RNA-binding proteins and messenger RNA transcripts to block a type of cell death called ferroptosis, which is driven by oxidative stress and iron accumulation. In blocking ferroptosis, these fragments protect neurons from degeneration. 

“Our findings suggest that neurons under toxic stress don’t passively wait to die,” says Arik Monash, Ph.D. student under the supervision of Professor Soreq. “This response could help explain the lasting effects of botulinum-based therapeutic treatments and might one day inform therapies for other neurodegenerative conditions.”  

The research paper titled “5′LysTTT tRNA fragments support survival of botulinum-intoxicated neurons by blocking ferroptosis” is now available in Genomic Psychiatry and can be accessed here. 
 

Researchers:
Arik Monash1,2,3, Nimrod Madrer2,4, Shani Vaknine Treidel2,4, Ofir Israeli5, Liad Hinden3, David S. Greenberg2, Joseph Tam3, Osnat Rosen6, and Hermona Soreq2,4 

Institutions:
1) Department of Biotechnology, Israel Institute for Biological Research (IIBR)
2) Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem
3) Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem
4) The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem
5) Department of Biochemistry and Molecular Genetics, IIBR
6) Department of Infectious Diseases, IIBR