New method to study key targets in Alzheimer's disease and prostate cancer

When designing a drug against a disease, chemists often used detailed plans of the proteins affected and against which the drugs must act. However, about a third of the proteins of our bodies have not yet been "photographed" because they generally vary in form, are in constant movements and have very little structure.This lack of "photographs" hinders the design of drugs against diseases involving proteins that are structurally "evasive," such as those in Alzheimer's disease and in prostate cancer that does not respond to conventional drugs.

With this new methodology, the group at IRB Barcelona, in collaboration with the University of Cambridge, will study why beta-amyloid plaques develop in Alzheimer's disease. They will examine the variety of forms that this protein adopts before and during accumulation. In another project, Salvatella will address the androgen receptor, the target protein in Kennedy's disease, a rare neurodegenerative disorder that causes muscular atrophy, as well in prostate cancer. "Oncologists are calling for new strategies to stop the growth of prostate tumours," explains Salvatella. The drugs currently available inhibit a part of the androgen receptor that is well known but in later stages of the disease these drugs can stop working. This protein has another important part that is intrinsically disordered and about which there is no structural information. "If our method is as reliable as we think, we could start to decipher the variety of structural forms that this other active part adopts in order to design drugs in the future."