A biophysical toolset to probe the microscopic processes underlying protein aggregation and its inhibition by molecular chaperones

Given the breadth and depth of the scientific contributions of Sir Christopher Dobson, with over 870 publications to date, it is inconceivable to convey in a single review the impact of his work and its legacy. This review therefore primarily focuses on his contributions to the development of strategies for preventing aberrant protein misfolding. The first section of this review highlights his seminal work on the elucidation of the microscopic nucleation processes underlying protein aggregation. Next, we discuss the specific inhibition of these steps by candidate drugs and biologics, with a particular emphasis on the role of molecular chaperones. In the final section, we review how protein aggregation principles can be exploited for the rational design of novel and more potent aggregation inhibitors. These milestones serve as excellent examples of the profound impact of Dobson's seminal work on fundamental science and its translation into drug discovery.