Tuesday, 22 October 2013

Switching on a light to solve the puzzle - finding a Parkinson's cure PART 2

...To cells...

Understanding the symptoms and progression of Parkinson's in patients is vital. However, it can only hint at the cause at the level of cells and genes. Work has to be done at the molecular and cellular levels to work out why nerve cells are dieing and therefore what can be done to counteract this. This would form the basis of a cure.

To work on nerve cells affected by Parkinson’s in the lab requires the development of reliable cells. Amazingly, human cells can be grown outside the body in single layers on the bottom of a petri dish. Even more amazing, skin cells can be grown and then converted into nerve cells that produce dopamine. Dr Elizabeth Hartfield has successfully produced and tested nerve cells grown from Parkinson’s patient skin cells. The nerve cells are equivalent to those cells that die in Parkinson’s. This is a very impressive feat and forms an invaluable resource to understand the proteins and processes inside cells that go wrong in Parkinson’s. Studies are underway investigating alpha synuclein and mitochondria (the energy factories of the cell), both implicated as causes of nerve cell death.

As with each torch that researchers use they have advantages and disadvantages; cells grown in layers are in two dimensions whereas the nerve cells in my brain make connections in three dimensions. This connectivity likely has important consequences for how nerve cells pass messages to each other.

...To the brain...

This is where another torch comes in: studying the next level of complexity in the brain relevant to Parkinson’s, the basal ganglia. Nerve cells in the substantia nigra send out long projections from their cell surface (called axons) to activate (via dopamine) another region in the basal ganglia called the striatum. This structure is important in initiating movement. In Parkinson’s sufferers there isn’t enough dopamine to activate the striatum resulting in movement problems.

Dr Stephanie Cragg presented fascinating data showing that there is more than one route taken by substantia nigra axons to activate the striatum. After a nerve cell is stimulated by an electrical impulse, dopamine is released from the end of the axon and receptors on nerve cells that make up the striatum grab hold of dopamine. As a result an electric impulse is generated in these initial striatum nerve cells, which is subsequently passed to other nerve cells in the striatum and beyond. Dr Cragg’s team has identified new receptors on striatum nerve cells that form an access point to the alternative route. It is hoped that this newly discovered route can be used to get more dopamine to the striatum to restore movement in Parkinson’s sufferers.

...To animal models...

Again, this torch has a disadvantage; the necessary focus on the striatum misses the affect on other parts of the brain and ultimately on movement and behaviour. Luckily, the link between what happens in the brain and its affect on complex movement can be addressed in model organisms such as mouse. Dr Richard Wade-Martins demonstrated that a human gene (e.g. alpha synuclein) can be inserted into mouse DNA and the resulting mouse will express the human gene. If the gene is faulty it will form the classical movement problems of Parkinson’s. Amazing! This allows researchers to follow what is happening in substantia nigra nerve cells and the affect this has on the movement of the mouse.

Animal models of Parkinson’s form a crucial stepping stone between understanding what’s happening in Parkinson’s affected cells and the movement symptoms in Parkinson’s sufferers like me. Work in animals like mice link the other three torches to make a powerful collective beam of light.

...To patients again...

Of course, humans are not big mice so any understanding extracted from the mouse will have to be tested in humans before the puzzle is solved and a cure given.

The road to a cure is long and complicated. But each piece that is added to the Parkinson's jigsaw by researchers like those at the OPDC, the closer a cure will become.

Please support research and Dave the worm! http://www.davetheworm.org/

OPDC http://opdc.medsci.ox.ac.uk/

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