Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

CNS neurons are endowed with the ability to recover from cytotoxic insults associated with the accumulation of proteinaceous aggregates in mouse models of polyglutamine disease, but the cellular mechanism underlying this phenomenon is unknown. Here, we show that autophagy is essential for the elimination of aggregated forms of mutant huntingtin and ataxin-1 from the cytoplasmic but not nuclear compartments. Human orthologs of yeast autophagy genes, molecular determinants of autophagic vacuole formation, are recruited to cytoplasmic but not nuclear inclusion bodies in vitro and in vivo. These data indicate that autophagy is a critical component of the cellular clearance of toxic protein aggregates and may help to explain why protein aggregates are more toxic when directed to the nucleus.

Original publication




Journal article


Proc natl acad sci u s a

Publication Date





13135 - 13140


Ataxin-1, Ataxins, Autophagy, Autophagy-Related Protein 12, Autophagy-Related Protein 5, Cell Line, Cell Nucleus, Cytoplasm, Humans, Huntingtin Protein, Huntington Disease, Microtubule-Associated Proteins, Models, Biological, Nerve Tissue Proteins, Nuclear Proteins, Peptides, Protein Transport, Proteins, Small Ubiquitin-Related Modifier Proteins, Spinocerebellar Ataxias, Transfection