Flinders Medical Centre Foundation
Flinders Medical Centre Foundation

Alzheimer's disease

 

World First for Parkinson's Team

A Link Between Down Syndrome And Alzheimer’s 

New Insights Into Parkinson’s Disease

Potential Treatment For Alzheimer's 

Parkinson's Enzyme May Help Alzheimer's  

 

World First for Parkinson's Team
First Published: Enews - April 2010
Updated:

 

A team of Flinders researchers are the first and only group in the world able to isolate the abnormal clusters of proteins which cause the death of brain cells in Parkinson's and related degenerative diseases.


Dr Wei Ping Gai, Senior Research Fellow in the Department of Human Physiology at Flinders Medical Centre, has been researching the causes of brain cell death in degenerative diseases for the past 20 years.


His research has had a particular focus on Lewy bodies - abnormal clusters of proteins which are found in the brain cells of both Alzheimer's and Parkinson's sufferers and in some types of dementia.


Dr Gai and his team have developed a world-first technique that uses antibodies attached to magnetic beads to bind to a particular protein (Alpha-synuclein) that is the largest component of Lewy bodies. They are then able to extract the Lewy bodies from Parkinson's affected brain tissue for detailed protein analysis.


This has allowed the Flinders team to be the first in the world to describe the internal structure of the Lewy body formations (which have a very precise structure), and to work in collaboration with teams from Elan Pharmaceuticals and Harvard Medical School to identify other proteins and components of the Lewy bodies.


The collaboration has recently uncovered that the addition or lack of phosphates on this target protein could play a role in the formation of the Lewy bodies. This interaction of this protein with the phosphates may also explain why the Lewy bodies react with the cell membrane to cause the cell's death.


The team hope that if they identify why proteins such as Alpha-synuclein form Lewy bodies, their research will pave the way for developing new diagnostic markers and drugs which can modify this process in both Alzheimer's and Parkinson's disease.

 

A Link Between Down Syndrome And Alzheimer’s
First Published: Investigator - February 2009
Updated:

 

A group of scientists based at Flinders Medical Centre are investigating a protein that is over-expressed in both Down syndrome and Alzheimer’s disease with the intent of identifying if there is a common link between these two conditions.

 

“Down syndrome is a genetically-based disorder which results in multiple conditions for sufferers,” said Dr Damien Keating, Head of the Molecular and Cellular Neuroscience Lab.

 

“Amongst these conditions, Down syndrome individuals normally develop Alzheimer's disease at an early age, often as young as their mid 30s or early 40s.”

 

Those born with Down syndrome have a trisomy (three copies) of the human chromosome 21 rather than the normal two.

 

This means that every cell in the body has an extra copy of the genes that make up chromosome 21, which leads to the symptoms and physical characteristics associated with Down syndrome.

 

One of the proteins that make up chromosome 21, called RCAN1, is over expressed in neurons in the brain of those with both Down syndrome and Alzheimer’s disease. Dr Keating has found that RCAN1 works as a regulator of a process called exocytosis which controls the firing of messages from one neuron to another (neurotransmission) in the brain.

 

Dr Keating’s lab, which is a leader in measuring cell signalling, has been testing different levels of RCAN1 expression and has discovered that both under and over expression of the protein reduces this neurotransmission.

 

This reduction of neurotransmission causes brain function and performance problems and can lead to brain cell death, as is often seen in both Down syndrome and Alzheimer’s.

 

“We hope to understand why changing the normal expression of RCAN1 affects neuron function and communication, to better understand what happens in the brain in conditions where RCAN1 levels are increased,” said Dr Keating.

 

“For example, could the risk of Alzheimer’s and the effects of Down syndrome be reduced by normalising the expression of RCAN1?”

 

Dr Keating and his team continue their investigations in the hopes of contributing to a better understanding of these conditions.

 

New Insights Into Parkinson’s Disease
First Published: Investigator - October 2005
Updated: World First for Parkinson's Team

 

Dr Wei Ping Gai, Senior Research Fellow in the Department of Human Physiology, and his team of researchers here at Flinders are focusing on the cause of brain cell death associated with Parkinson’s.

 

Sufferers of Parkinson’s experience a range of symptoms that affect the sensory system, musculature problems such as body tremors and stiffness, and psychological difficulties such as depression, panic attacks and fatigue.

 

This disease largely affects the elderly community, however of the thousands of Australians diagnosed each year, approximately 10% are under the age of 40.

 

A recent discovery into the processes behind this disease has found that a typically normal protein, alpha-synuclein (AS), acts as a major component in the creation of Lewy bodies, abnormal clusters of proteins within nerve cells in the brain. This toxic substance has been linked to the brain cell death associated with the development of degenerative brain diseases such as Parkinson’s, Alzheimer’s and Dementia.

 

Working with the human brain Dr Gai and his team of researchers are keenly interested in the reactions that take place within this AS protein, which are caused by outside antagonists such as gene mutation or environmental factors, leading to the toxicity that causes brain cell death.

 

For many years Dr Gai has undertaken a great deal of research into the abnormal brain matter associated with neurodegenerative diseases. During this time two new elements were discovered that seem to play major roles in Parkinson’s and similar diseases.

 

A molecule LRRK2 was found to have a detrimental effect on the brain and more importantly an ubiquitin, a protein that marks unhealthy proteins for destruction, was also found.

 

“We found that this ubiquitin somehow specifically labels the aggregated protein AS for destruction,” says Dr Gai.

 

Further research is hoped to be undertaken here at Flinders in the near future to investigate the interactions that take place between these three important factors; the alpha-synuclein protein, the LRRK2 molecule and the ubiquitin, within Parkinson’s disease.

 

This research could provide another stepping stone in ascertaining the mechanisms behind Parkinson’s and other similar debilitating diseases. It will also provide new information in the use of antibodies for better diagnosis and treatments.

 

Potential Treatment For Alzheimer's
First Published: Investigator - August 2005
Updated:

 

Researchers at Flinders Medical Centre are investigating a nerve receptor within the brain, known as P75, that could be used to block and destroy a toxic peptide identified as one of the main protagonists of Alzheimer’s.

 

Scientists have found that due to a genetic mutation and/or environmental factors, toxic amyloid-beta peptides accumulate in the brain which in turn threaten healthy nerve cells in the surrounding areas. Once these toxic peptides are produced, a structure called plaque forms in the brain which leads to Alzheimer’s.

 

Dr Xin-Yu Zhou, Associate Professor and Senior Research Fellow from the Department of Physiology at Flinders Medical Centre, who has been studying the receptor for over 10 years, has observed through his experiments that an increase of this receptor’s chemical affects nerve death which occurs in Alzheimer’s.

 

Dr Zhou and his team are looking at a way of removing this toxic peptide by using a biological chemical derived from the P75 nerve receptor which may also have the effect of blocking the toxic effects of the peptide on nerves.

 

Further research into nutrients (Omega 3 and an ancient Chinese herbal remedy Schisandra Chinensis) and their effects on the toxic peptide are also planned to be undertaken as a counterpart to the current P75 research in the near future.

 

“There is no fundamental therapy on the market today for this disease” says Dr Zhou. Fellow researcher Dr Yan-Jiang Wang agrees that the current therapies are temporary symptom treatments and do not provide the community with a reliable long term result.

 

While still in its early stages the research that the Flinders Medical Centre Foundation has funded will hopefully lead to finding a reliable and more efficient treatment for those who suffer from the effects of Alzheimer’s Disease.

 

Parkinson's Enzyme May Help Alzheimer's
First Published: Investigator - January 2003
Updated:

 

Parkinson's disease is a devastating brain disease that effects a significant proportion of our ageing population.

 

Although we don't know the cause of this disease there is a large body of evidence to suggest that oxidative stress is a major factor.

 

For some reason as yet unknown, the brain cells in a part of the brain involved in motor control, start to die leading to movement problems.

 

Dr John Power and Dr Weiping Gai and their team from the Department of Human Physiology at Flinders Medical Centre have been researching the affects of oxidative stress on brain enzymes and have discovered a new enzyme at work in the brains of sufferers of Parkinson's disease.

 

A paper detailing their findings was published in September 2002 in the highly accredited American Journal of Pathology.

 

"We have recently shown that brain cells under oxidative stress start to turn on a new anti-oxidant enzyme to try and protect themselves. In addition, other supporting cells also start making more of this enzyme.

 

In an exciting development since the paper was presented, Dr Power and his team have found evidence to support that the enzyme has a role in Alzheimer's - although it appears to be different from Parkinson’s disease. For example, in Alzheimer’s disease regions that did not seem to make this enzyme appeared to be more susceptible to oxidative damage and have more pathology.

 

"We are the only team in the world that has shown that the enzyme is present in the brain as well as being involved in Parkinson's and Alzheimer's.

 

"A grant from the Foundation has helped keep this research alive. The next step for the team is to acquire funding for a diagnostic test so that further exciting research can occur." said Dr Power.

 

 
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