Assistant Professor Reut Shalgi
The accumulation of protein aggregates is a hallmark of a number of neurodegenerative disorders, including Alzheimer’s, Huntington’s, and Parkinson’s disease (AD). One of the prominent hallmarks of these protein aggregates is the sequestration of components of the protein quality control (PQC) system. The PQC system is the guardian of proteins in the cell, maintaining and regulating proper balance between protein production, protein, protein trafficking and protein degradation.
Recently, we found a novel form of cross-talk between the PQC system and the translational machinery. During cellular stress a novel mode of regulation is involved in global inhibition of protein production: a so called near universal translation elongation pausing. Strikingly, we found that chaperones, proteins that are part of the quality control system are involved in the inhibition of protein production. Therefore, chaperones, as natural sensors of protein aggregation, are also able to communicate the cellular status to the protein production machinery.
Here we propose to study the role of aberrations in the control of protein production in Alzheimer’s disease. As a consequence of toxic Amyloidβ aggregation and chaperone sequestration, protein production may be impaired.