The misfolding and aggregation of proteins is a common hallmark of neurodegenerative disorders, such as Alzheimer's, Parkinson's and Huntington's disease. The latter is caused by genetic expansion of the huntingtin (Htt) gene, which results in the addition of tracts of polyglutamine (polyQ) to the protein, leading to toxic HTT aggregates in the brain. Recently, intercellular propagation of protein misfolding has emerged as an important means for the spreading and transmission of these diseases. However, little is known with regard to how HTT aggregates progress through the brain. Chiara Zurzolo and colleagues (p. 3678) now investigate the capability of mutant HTT fragments to transfer between co-cultured neuronal cells in primary neuronal culture. They demonstrate that HTT aggregates formed in donor cells are spontaneously transferred to receiving cells; this transfer appears to be an active transport mechanism that requires cell–cell contact. Interestingly, the authors find HTT aggregates in tunneling nanotubes (TNTs), which they had previously shown to be involved in the spreading of prions. They show here that their numbers increase when cells express mutant, but not wild-type HTT fragments. On the basis of these data, the authors suggest that TNTs provide an efficient mechanism for the transfer of polyQ aggregates between neuronal cells, which might also be exploited to develop new avenues for the therapeutic intervention of different neurodegenerative diseases.
- © 2013. Published by The Company of Biologists Ltd