Coffee’s clue to Parkinson’s treatment
7 Oct 2011 by Evoluted New Media
Our morning cup of coffee might do more than perk us up in the morning – caffeine contained in our morning pick-me-up could pave the way for a new generation of target drug treatments.
While caffeine itself may not make a very effective drug to treat neurological diseases, its parent compound xanthine – and its derivatives – are potential targets.
Xanthine-based drugs such as caffeine are known to inhibit the action of adenosine A2A receptors, but the exact molecular mechanism involved was not fully understood. A visit to the Microfocus Macromolecular Crystallography (MX) beamline at Diamond Light Source has helped scientists from Heptares Therapeutics reveal the receptor’s structure.
The adenosine A2A receptor is involved in the regulation of neurotransmitters in the brain, cardiovascular and immune system, and scientists have now shown how xanthine-based drugs bind to this target.
“These co-structures of xanthenes in complex with the adenosine A2A receptor advance our understanding of what is happening at the molecular level when the drug binds to its target and blocks the receptors response,” said Dr Fiona Marshall, chief scientific officer at Heptares.
“Along with novel chemotypes discovered by our team, the structural data we collected at Diamond is enabling us to develop highly optimised next-generation drug candidates for Parkinson’s disease and other neurological disorders.”
The adenosine A2A receptor is a G-protein-coupled receptor (GPCR), of which there are over 700 variants encoded in the human genome. As many as 75 of these have clinical validation, presenting a wide range of opportunities as therapeutic targets in cancer, diabetes obesity and pain.
“GPCRs represent the single most important family of drug targets in the human body because they are central to so many biological processes,” said Dr Andrew Doré, senior scientist.
“The design of drugs for GPCRs is hampered by the lack of structural information so access to a facility like the Diamond synchrotron is vital to our research. It has enabled us to solve the 3D structure of the adenosine A2A receptor in complex with caffeine and other xanthines as well as our own novel drug candidates.”
Structure of the adenosine A2A receptor in complex with ZM241385 and the xanthenes XAC and caffeine
