Tali Gidalevitz

Protein misfolding diseases, such as Alzheimer's or Parkinson's diseases, ALS, or certain types of diabetes are becoming increasingly prevalent in the aging human population. Protein misfolding is often implicated in these disorders, but the mechanisms remain unclear. We have shown that misfolding and aggregation of disease-related proteins (e.g. polyglutamine expansions in Huntington's disease, or mutant SOD1 in ALS) can trigger misfolding of other metastable 'bystander' proteins, causing their loss of function and thus disrupting cellular functions. On the other hand, these metastable proteins, encoded by genetic polymorphisms, strongly modulate the disease phenotypes. We proposed that competition for the folding resources underlies this toxic behavior. It is currently thought that understanding such failure of protein homeostasis (proteostasis) is key to understanding and combating aging and neurodegeneration. My lab focuses on mechanisms that control proteostasis, using genetic, biochemical, and live imaging approaches in a metazoan C. elegans and mammalian neurons.