Boosting protein quality control systems to treat neurodegenerative diseases

The deposition of misfolded proteins is a defining feature of many age-dependent human diseases, including the increasingly prevalent neurodegenerative diseases. Why aggregation-prone proteins accumulate in aged cells remains largely unclear. Cells normally strive to ensure that proteins get correctly folded and have powerful and sophisticated mechanisms to maintain homeostasis under adverse conditions. However, with age, the cellular defence systems against misfolded proteins gradually fail, leading to the accumulation of misfolded proteins with devastating consequences for cells and organism.

In principle, improving the cells’ ability to deal with misfolded proteins should represent a generic approach to reduce the pathology in diverse protein misfolding diseases. My lab has identified powerful strategies to improve the cells’ ability to deal with misfolded proteins and implemented one of such strategy in mice to safely prevent two unrelated neurodegenerative disease. Some of the approaches we work on shed light on fundamental cell biological processes, while others pave the way to rationale therapeutics. Our work demonstrates that generic approaches aimed at helping cells to survive protein quality control failures can be useful to prevent protein misfolding diseases, including the devastating neurodegenerative diseases.

Various projects are available ranging from biochemistry, structural biology, cell biology and animal models of neurodegenerative diseases. Further information may be obtained from Dr Anne Bertolotti– email: aberto@mrc-lmb.cam.ac.uk