We are part of the Faculty of Medicine and Sagol School of Neuroscience at Tel Aviv University.
Our research utilizes state-of-the-art technologies to elucidate cellular mechanisms of neurological disorders. Some of these diseases progress late in life, such as Huntington's disease and Parkinson's disease.
A common characteristic of these diseases is the accumulation of proteins that are not folded properly and can form aggregates in cells.
We aim to elucidate novel regulatory pathways of protein homeostasis in cells to better understand the basis of these devastating diseases and to identify future therapeutic targets.
Our review on ubiquitin signaling and aggregate-prone proteins is out
Parkinson's disease spotlight
Molecular Cell 73, 5-6
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.