Test your metal: Platinum-containing molecules show promise as future treatments for Alzheimer's disease
28 May 2008
Scientists based in Australia have produced a group of molecules able to bind to and block the harmful effects of the amyloid beta peptide - the molecule that forms damaging plaques in the brains of people with Alzheimer’s disease. This class of compounds, currently under further development by the team, could lead to new drugs to treat this debilitating disease.
The researchers set out to design molecules that would prevent two processes thought to be involved in the development of Alzheimer’s disease.
Firstly, the target molecule would block the formation of the amyloid fibrils, which create plaques in the brain in Alzheimer’s disease. Secondly, the molecule would prevent the metal copper from binding to the amyloid beta peptide - a process that researchers think can generate so-called reactive oxygen species, which are toxic to brain cells.
The molecules developed were based on cisplatin, an anticancer drug that has been in use for over 30 years. Like cisplatin, all molecules developed contained the metal platinum, which the researchers thought would bind to the metal binding site on the amyloid beta peptide.
The team tested three platinum-based molecules able to bind the beta amyloid peptide and block its inhibitory effect on the communication between neurons in mouse brain slices. The researchers are now working on these molecules to try and produce more potent versions that can cross the blood brain barrier easily, for use as therapeutics.
The research team from the University of Melbourne, Australia included Dr David P Smith, now based at the University of Leeds, whose work in Australia was funded by the Wellcome Trust.
References
Barnham KJ et al. Platinum-based inhibitors of amyloid-beta as therapeutic agents for Alzheimer’s disease. Proc Natl Acad Sci U S A 2008;105(19):6813-8.