Scientists have discovered that neurons exposed to Botox (botulinum toxin A) don’t just survive—they fight back. A new study shows that tiny fragments of tRNA, a type of genetic material, help protect nerve cells by blocking a specific kind of cell death called ferroptosis, which is caused by stress and iron buildup in the body. This breakthrough explains why Botox paralyzes muscles without killing the neurons that control them—and could lead to longer-lasting, more precise medical and cosmetic uses of the toxin.

[Hebrew University of Jerusalem]– A new study led by PhD student Arik Monash, under the supervision of Professor Hermona Soreq from The Edmond and Lily Safra Center for Brain Sciences (ELSC) at The Hebrew University of Jerusalem, Professor Joseph Tam from the School of Pharmacology and Dr Osnat Rosen from the Israeli Institue of Chemical Defense, reveals how a unique class of small RNA fragments helps neurons resist the damaging effects of botulinum neurotoxin A (BoNT/A)—the world’s most potent known biological toxin.
Although BoNT/A blocks nerve-muscle communication and induces temporary paralysis, it paradoxically avoids killing the neurons it affects. This dual nature underpins both its dangers and its widespread use in medical and cosmetic procedures. Yet until now, the molecular basis for this neuron survival remained unknown.

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,” said Monash. “They actively deploy RNA fragments to push back against death signals. This response could help explain the lasting effects of botulinum-based therapeutic treatments and might one day inform therapies for other neurodegenerative conditions.”

Further analysis revealed that these protective RNA fragments often share an 11-nucleotide sequence motif, which enhances their ability to silence genes involved in both cell death and cholinergic signaling. This motif was found in both human cell cultures and in rat tissues, suggesting an evolutionarily conserved mechanism for neuronal defense.

Professor Soreq, who supervised the research, explained, “We’ve known for years that botulinum toxin paralyzes muscles without destroying the neurons that control them—but we never fully understood why. 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.”