Current research: what causes Parkinson's?

We are currently funding 37 research projects worth over £5million exploring the causes of Parkinson's.

We need to know how and why certain nerve cells in the brain in Parkinson's die in order to find a cure.

In Parkinson's there is a slow loss of nerve cells in the brain, with symptoms only emerging when around 70% of cells have been lost.

But we still don't know how or why these nerve cells die.

 

Featured research projects

The Monument Discovery Award

The Monument Discovery Award is our biggest ever research grant at £5million over 5 years.

The project ultimately aims to find a cure for Parkinson's - to develop treatments that allow everyone to live free from the symptoms of the condition.

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Investigating changes in the alpha-synuclein protein and its potential role in Parkinson's

• Dr Mark Cooper, Institute of Neurology, UCL
• £208,751 over 3 years
• Start date: tbc

This project will investigate how changes in the alpha-synuclein protein influence the development of Parkinson's.

An abnormal form of the alpha-synuclein protein is found at high levels inside the Lewy bodies, or sticky protein clumps, which clog up the nerve cells affected in Parkinson's.

The abnormal alpha-synuclein has an extra phosphate molecule tag. This seems to change the way cells handle dopamine, the chemical messenger lost in the Parkinson's brain.

Pinpointing how these changes in alpha-synuclein affect how the nerve cells work will promote the development of new and better treatments that can help the nerve cells affected in Parkinson's to work better for longer.

Developing and using a new worm model for Parkinson's

• Dr Anton Gartner, University of Dundee
• £196,322 over 3 years
• Start date: February 2010

Dr Gartner's project will use the worm C. elegans to study key genes that cause cells to die. Understanding how genes damage or protect nerve cells may provide crucial clues to what happens when nerve cells die in Parkinson's.

Worms share many genes with humans that are known to be involved in Parkinson's, and provide a simple and cheap system to study how nerve cells work.

The research team will focus on investigating how the LRRK2 gene works, which is overactive in many people with Parkinson's. They will also use the worms to test potential new drugs designed to combat the effects of the LRKK2 gene.

News story: Worms may hold clue to inherited Parkinson's

The role of inflammation in the development of Parkinson's

• Dr Matthew Wood, University of Oxford
• £116,958 over 2 years
• Start date: January 2010 

Inflammatory changes inside the brain may be involved in the death of nerve cells in Parkinson's. Inflammation gives rise to harmful molecules, known as free radicals, that can damage cells through the process of oxidative stress.

This project will investigate how the free radical nitric oxide, which is generated through inflammation, is involved in the development of Parkinson's.

Ultimately, this research could identify potential new treatments that combat inflammation in the Parkinson's brain.

Using yeast cells to examine the role of the DJ-1 gene

• Dr Flaviano Giorgini, University of Leicester
• £242,759 over 3 years
• Start date: November 2009

We know that the DJ-1 gene is involved in some inherited forms of Parkinson's. But we don't understand how mutations in this gene affect the nerve cells in Parkinson's.

This study will explore how healthy and faulty versions of DJ-1 gene affect yeast cells, which will provide crucial clues to how Parkinson's develops.

Yeast models are incredibly useful for studying genes. They provide researchers with a simple system in which to study how individual genes work.

This research may also uncover new mechanisms by which drugs could halt or even reverse the progression of Parkinson's.

How does the DJ-1 gene protect nerve cells from damage?

• Dr Gyorgy Szabadkai, University College London
• £262,892 over 3 years
• Start date: November 2009 

DJ-1 is one of several genes known to be linked to Parkinson's. Research has shown that healthy DJ-1 has a protective role and can prevent nerve cells from dying. However, if the DJ-1 gene is faulty and doesn't work properly, it can lead to the onset of Parkinson's.

This project will examine how DJ-1 safeguards against the toxic chemicals that can build up inside nerve cells. These harmful chemicals damage cells in a process known as oxidative stress which can lead to cell death.

By looking in detail at how DJ-1 behaves, this study may identify key new drug targets that could protect against cell death.

News story: New funding for research into the genetic causes of Parkinson's

Producing an online catalogue of genetic changes in Parkinson's

• Professor John Hardy at the Institute of Neurology, UCL
• £163,668 over 3 years
• Start date: October 2009

Genetic studies are revealing new genes that affect the risk of developing Parkinson's. These 'risk' genes may not always change the way proteins inside cells work, but rather they change the amount of proteins that are actually produced inside cells.

Professor Hardy's team aims to produce a catalogue which will provide information about all of the different genetic changes that have been found inside the brain area affected in Parkinson's.

This comprehensive directory of genetic changes will be available online for researchers throughout the world studying genes associated with Parkinson's - providing a

How do changes in the PINK1 gene lead to nerve cell death?

• Professor Dario Alessi, University of Dundee
• £84,945 over 3 years
• Start date: October 2009

Studying families with inherited forms of Parkinson's have shown that changes in the PINK1 gene increase the risk of developing the condition. However, how and why this happens is unclear.

Understanding how changes in the PINK1 gene make nerve cells more vulnerable will help develop new treatments that tackle the problems directly.

In this project the research team will compare cells that have either healthy or abnormal PINK1 to create a map of all the activities that PINK1 is involved in.

Looking at post-mortem brain tissue from people with Parkinson's with and without PINK1 mutations will help confirm their findings and to build a picture of why nerve cells die in Parkinson's.

A zebrafish model of early onset Parkinson's

• Dr Oliver Bandmann, University of Sheffield
• £239,593 over 3 years
• Start date: June 2009

Changes or mutations in the parkin gene are linked to some forms of early-onset Parkinson's. But we don't know how these changes in parkin lead to the death of nerve cells in Parkinson's.

In this study the parkin gene will be removed from zebrafish, to create a new animal model for Parkinson's. Looking at the difference that this makes to the nerve cells and how they work, will help us understand how defects in the human parkin gene result in Parkinson's.

Ultimately, it may be possible to use these zebrafish to screen for new drugs that could slow down the progression of Parkinson's.

News story: New research using zebrafish may hold clue to early-onset Parkinson's

Investigating changes in dopamine release in Parkinson's

• Dr Bazbek Davletov, University of Cambridge
• £99,946 over 2 years
• Start date: June 2009

Dopamine, a chemical that relays messages between nerve cells, is depleted in the brains of people with Parkinson's. The protein alpha-synuclein, a key player in Parkinson's, is thought to be involved in controlling the release of dopamine.

This project will investigate how alpha-synuclein controls dopamine release from nerve cells, and if this changes in the early stages of Parkinson's.

The study aims to shed new light on why the dopamine-releasing nerve cells stop working properly in Parkinson's. This will help us develop drugs that can slow, halt or reverse the progression of the condition.

News story: New funding for University of Cambridge to shed light on why nerve cells die

Why are dopamine-producing nerve cells vulnerable in Parkinson's?

• Dr Siew-Lan Ang, National Institute Medical Research, London
• £189,017.03 over 3 years
• Start date: September 2009

In Parkinson's, the dopamine-producing nerve cells found in the region of the brain called the substantia nigra die. Dopamine is a chemical inside the brain involved in relaying messages that instruct the body to move.

However we do not understand why these particular nerve cells in this specific brain area are so susceptible in Parkinson's.

This project will study the early stages of the development of the dopamine-producing nerve cells. This may provide vital clues to why nerve cells in the substantia nigra are most vulnerable to damage as they get older.

This project will shed light upon why such a specific population of cells is susceptible to the damage that causes Parkinson's - leading to the development of drugs that can protect these vulnerable cells and slow the progression of the condition.

How do mutations in the PINK1 gene cause Parkinson's?

• Dr Andrey Y Abramov, Institute of Neurology
• £298,345 over 3 years
• Start date: May 2008

The PINK1 gene, one of 5 associated with inherited Parkinson's, was first discovered in 2004 by scientists we funded.

This study, at the Institute of Neurology, is looking at how these mutations in the PINK1 gene affects nerve cells, making them vulnerable and more likely to die.

News story: New funding for research on role of PINK1 gene

Investigating a new mouse model for Parkinson's

• Dr Lynn Bedford, University of Nottingham
• £441,964 over 5 years
• Start date: January 2008

Dr Bedford is using a new mouse model to investigate the changes that occur inside the brain in Parkinson's. Better models that truly reflect Parkinson’s are urgently needed for developing new treatments that can stop, slow or reverse the progression of the condition.

This new mouse model was created by the team by altering specific genes to produce some of the main features of Parkinson's.

In particular, the team will be investigating the formation of Lewy bodies, clumps of sticky proteins that clog up the nerve cells affected by Parkinson's.

This will help scientists find ways to stop this happening, and ultimately prevent the spread of Lewy bodies through the brain as the condition progresses.

Investigating the inner-workings of nerve cells in Parkinson's

• Dr Philip Robinson, St James's University Hospital, Leeds
• £157,704 over 3 years
• Start date: October 2007

We know that the nerve cells affected in Parkinson's contain too much of a protein called alpha-synuclein. They also have problems with their mitochondria, the tiny batteries responsible for producing the essential energy cells need to do their work.

This project is investigating how alpha-synuclein and mitochondria interact inside the nerve cells affected by Parkinson's.

Understanding more about what is happening deep inside the brain in Parkinson's will help us develop more effective treatments that target the root cause of the condition.

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