Work

From Gut to Systemic Circulation: Molecular Strategies of Botulinum Neurotoxin Complexes

Year: 2026

Type: article

Abstract: Botulinum neurotoxins (BoNTs), among the most potent biological toxins, rely on co-produced nontoxic proteins to survive harsh gastrointestinal conditions and achieve efficient systemic dissemination after oral exposure. Recent structural and functional studies have revealed how BoNTs bind to the nontoxic non-hemagglutinin (NTNH) factors to engage in interactions with either OrfXs/P47 or hemagglutinins (HAs) components for systemic dissemination. This review synthesizes recent findings that elucidate the molecular basis of NTNH-specific anchoring to the HA70 triskelion-like element or to the host protease-activated form of OrfX2, thereby highlighting divergent pathways that enhance oral toxicity. We also discuss current perspectives on the molecular mechanisms through which BoNTs, in cooperation with associated nontoxic proteins, are absorbed from the intestine.

Source: Toxins

DOI: 10.3390/toxins18030116

Authors: Juliette Mondy, Emmanuel Lemichez

Institutions: Centre National de la Recherche Scientifique, Inserm, Institut Pasteur, Université Paris Cité, Microbiologie Intégrative et Moléculaire

Language: English

Topic: Botulinum Toxin and Related Neurological Disorders

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,258