UKPDSTB General: Brain Bank Bulletin issue 5, page 2

Page 2 of 4

Brain Bank Bulletin

Issue 5

Winter 2005

Inside this issue:
Tissue Bank collects its 100th brain!	1	Running for the PDS	1	Drug Targets for Treatment	2	Number of donations	2	PDS Research Agenda	3
Registered Donors	4	Contact Information	4	Future Branch Talks	4	Notices	4	Our Team	4

Identifying new drug target for Parkinson’s treatments from research findings from donated brain tissue.

In the past twenty years there has been an extensive amount of research utilising donated human brain tissue in an attempt to understand why the cells in the Parkinson's brain are dying. A significant amount of this work in the UK has been funded by the Parkinson's Disease Society. From this work scientists have been able to start to put together a complex picture of many different factors, all, or some of which may seriously affect the well being of brain cells and cause them to die. Of these, three areas have received extensive scientific support. Firstly, in Parkinson's there is a defect in the mitochondria, the power stations in our cells that provide the energy to keep our cells alive. Secondly, there have been defects detected in the proteasome, a complex in our cells that handles and removes defective proteins that would otherwise be toxic to the cells. Thirdly, a process called oxidative stress has been implicated where toxic chemicals called "free radicals" interact with and damage many components of our cells. These components include the membrane that cover the cells, the vital proteins that form the building blocks of cells and our genetic information that encodes for everything the cells needs to keep it functioning normally. Although it is not fully understood how these three defective systems interact together, they are all potential targets for the development of drugs to stop them happening in order to protect the cells from dying. Here at Imperial we have been concentrating on the oxidative stress pathway and trying to find out whether we can neutralise these damaging free radicals.

Free radicals are not all bad, indeed our body uses them to kill off bacteria that cause infections but when they are produced in excessive amounts then they can cause damage to our own cells. Our bodies use molecules called antioxidants, many derived from our diet e.g. vitamin C and E, to neutralise free radicals and prevent their damaging effects. Unfortunately, one of the main antioxidants in the brain, a molecule called glutathione, is deficient in the Parkinsonian brain. Hence, we have been testing other antioxidants to see whether they could possibly be used as a treatment to stop the cells from dying in the Parkinson’s brain. One such group of antioxidants that have shown promising results in tests, are a group of molecules called flavonoids, they also occur in nature, for example in fruits, vegetables, seeds, grain, tea and red wine, but it is only now that we are realising that they may have medical uses. Not only do these flavonoids potently neutralise the free radicals but we have recently demonstrated that some flavonoids can boost the brains own antioxidant defence systems giving it a greater ability to fight off free radical damage. In animal models of Parkinson’s disease we have shown that some flavonoids are capable of not only protecting the nerve cells of the brain against toxins but also they can revive sick and dying nerve cells. Obviously, such studies require further validation before they can be tested on patients but they do highlight how work on donated brain tissue often points the way in developing new drugs to combat Parkinson's.

Dr David Dexter