Our research utilizes state-of-the-art technologies to elucidate cellular mechanisms of neurological disorders with a particular focus on tri-nucleotide repeat expansion diseases and Parkinson’s disease. Some of these disorders progress late in life, such as Huntington's disease and Parkinson's disease. A common characteristic in these disorders is the accumulation of proteins that are not folded properly and can form aggregates in neurons. Using patient bio specimens, stem cells and mouse modeling, we aim to elucidate novel regulatory pathways of protein homeostasis inside and outside the brain to better understand the basis of these devastating diseases and to identify future therapeutic targets.

Name: Avraham Ashkenazi
Address: IL

Recent lab news

Our EMBO Journal paper is published !

Our review on autonomic nervous system disorders is out

Autophagy, ubiquitin and polyglutamine diseases

Nature 545, 108–111

Expanded polyglutamine (polyQ) tracts in different proteins are a common feature of many neurodegenerative diseases. Many normal proteins also carry these tracts, although their function remains unclear. We show that polyQ tracts in a normal ataxin protein have a role in the degradative process of autophagy. In this case, the polyQ domain allows ataxin 3 interaction with the autophagy mediator beclin 1. Ataxin 3 can thus deubiquitinate beclin 1, preventing its degradation by the proteasome and allowing it to initiate autophagy. We not only demonstrate the relevance of our findings to the process of autophagy in neurons, but also show how, under disease conditions, the polyQ tracts in mutant proteins compete with those in ataxin 3 to prevent beclin 1 stabilization and so impair starvation-induced autophagy.