A team of Weizmann scientists has gained new insight into a recently approved Alzheimer’s drug called rivastigmine (currently sold as Exelon (TM)), revealing its molecular mechanism.
“The results were surprising,” says Prof. Joel Sussman of the Structural Biology Department. “They show that we can safely treat Alzheimer’s disease with much lower quantities of rivastigmine, thus minimizing adverse effects.”
Rivastigmine, like other Alzheimer’s drugs, works by blocking the action of an enzyme involved in Alzheimer’s disease called acetylcholinesterase (AChE). The scientists – Sussman, Prof. Israel Silman of the Neurobiology Department and Ph.D. student Pazit Bar-On – took complex “snapshots” of rivastigmine bound to AChE.
They then built a molecular map showing the spatial arrangement of all the atoms of AChE and rivastigmine. Using this map, they found that after binding to AChE the rivastigmine molecule breaks in two and moves some of AChE’s atoms, making it difficult for AChE to return to an active state. It thus prolongs the drug’s effect.
Prof. Israel Silman is the incumbent of the Bernstein-Mason Professorial Chair of Neurochemistry. His research is supported by the Nella and Leon Benoziyo Center for Neurosciences; the Charles A. Dana Foundation; the Carl and Micaela Einhorn-Dominic Brain Research Institute; and the Helen and Milton A. Kimmelman Center for Biomolecular Structure and Assembly.
Prof. Joel Sussman is the incumbent of the Morton and Gladys Pickman Chair in Structural Biology. His research is supported by the Charles A. Dana Foundation; the Jean and Jula Goldwurm Memorial Foundation; the Helen and Milton A. Kimmelman Center for Biomolecular Structure and Assembly; the Joseph and Ceil Mazer Center for Structural Biology; and the late Sally Schnitzer.