Back to overview

Transneuronal propagation of mutant huntingtin contributes to non-cell autonomous pathology in neurons.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2014
Author Pecho-Vrieseling Eline, Rieker Claus, Fuchs Sascha, Bleckmann Dorothee, Esposito Maria Soledad, Botta Paolo, Goldstein Chris, Bernhard Mario, Galimberti Ivan, Müller Matthias, Lüthi Andreas, Arber Silvia, Bouwmeester Tewis, van der Putten Herman, Di Giorgio Francesco Paolo,
Project Entwicklung und Funktion von motorischen Netzwerken
Show all

Original article (peer-reviewed)

Journal Nature neuroscience
Volume (Issue) 17(8)
Page(s) 1064 - 1072
Title of proceedings Nature neuroscience
DOI 10.1038/nn.3761


In Huntington's disease (HD), whether transneuronal spreading of mutant huntingtin (mHTT) occurs and its contribution to non-cell autonomous damage in brain networks is largely unknown. We found mHTT spreading in three different neural network models: human neurons integrated in the neural network of organotypic brain slices of HD mouse model, an ex vivo corticostriatal slice model and the corticostriatal pathway in vivo. Transneuronal propagation of mHTT was blocked by two different botulinum neurotoxins, each known for specifically inactivating a single critical component of the synaptic vesicle fusion machinery. Moreover, healthy human neurons in HD mouse model brain slices displayed non-cell autonomous changes in morphological integrity that were more pronounced when these neurons bore mHTT aggregates. Altogether, our findings suggest that transneuronal propagation of mHTT might be an important and underestimated contributor to the pathophysiology of HD.