Research file
Study: Freezing of gait (walking movement) in Parkinson’s disease may be a problem of space perception.
Researcher: Chad A. Lebold, master of science graduate in Wilfrid Laurier University’s department of kinesiology and physical education.
Study focus: Lebold designed experiments to determine the underlying causes of motor freezing episodes experienced by some Parkinson’s disease patients, along with the cues that could lead to an improved quality of life.
His research project was called: Freezing of Gait in Parkinson’s Disease: A Perceptual Cause for a Motor Impairment?
“Our goal was to challenge current beliefs that freezing is a motor impairment, instead suggesting that patients are having problems with space perception because of sensory-perceptual issues that interfere with movement,” Lebold said.
Lebold examined the gait of three different groups of subjects — those with Parkinson’s disease and freezing episodes, those with Parkinson’s disease but no freezing, and a control group) as they walked toward doorways of varying widths. The goal was to determine how their behaviour was affected by doorway size.
Parkinson’s patients who experience freezing episodes showed the greatest change in gait as they approached the narrow doorway, with more gait variability, shorter steps and widening their base of support.
“Combining visual feedback aids in perceptually demanding conditions gave us a greater understanding of the deficits associated with gait in Parkinson’s disease,” Lebold said.
“We were surprised to find that even Parkinson’s patients who do not experience freezing were influenced by the perception of a narrow doorway and exhibited behaviours similar to those with freezing.”
The study emphasized the importance of thinking outside the box and questioning what the underlying mechanism for clinical motor impairments might be, said Quincy Almeida, study co-author and an associate professor of kinesiology and physical education, as well as director of the Sun Life Financial Movement Disorders Research and Rehabilitation Centre.
“The results of this research hopefully will provide a greater understanding of one of the most debilitating disorders associated with Parkinson’s disease,” Lebold said.
“The findings could also impact the direction of future research, hopefully leading to successful intervention and prevention strategies for gait disorders.”
Future research will determine the specific aspects of the doorways that affect subjects’ walking patterns.
For more information go to www.parkinsonresearchfoundation.org
Sunday, December 27, 2009
Sunday, December 13, 2009
New therapy targets for amyloid disease
A major discovery is challenging accepted thinking about amyloids – the fibrous protein deposits associated with diseases such as Alzheimer's and Parkinson's – and may open up a potential new area for therapeutics.
It was believed that amyloid fibrils - rope-like structures made up of proteins sometimes known as fibres - are inert, but that there may be toxic phases during their formation which can damage cells and cause disease.
But in a paper published today [04 December 2009] in the Journal of Biological Chemistry, scientists at the University of Leeds have shown that amyloid fibres are in fact toxic - and that the shorter the fibre, the more toxic it becomes.
"This is a major step forward in our understanding of amyloid fibrils which play a role in such a large number of diseases," said Professor Sheena Radford of the Astbury Centre for Structural Molecular Biology and the Faculty of Biological Sciences.
"We've revisited an old suspect with very surprising results. Whilst we've only looked in detail at three of the 30 or so proteins that form amyloid in human disease, our results show that the fibres they produce are indeed toxic to cells especially when they are fragmented into shorter fibres. "
Amyloid deposits can accumulate at many different sites in the body or can remain localised to one particular organ or tissue, causing a range of different diseases. Amyloid deposits can be seen in the brain, in diseases such as Parkinson's and Alzheimer's, whereas in other amyloid diseases deposits can be found elsewhere in the body, in the joints, liver and many other organs. Amyloid deposits are also closely linked to the development of Type II diabetes.
Professor Radford said: "Problems in the self-assembly process that results in the formation of amyloid are a natural consequence of longer life. In fact 85 per cent of all cases of disease caused by amyloid deposits are seen in those over the age of sixty or so."
The study was funded by the Wellcome Trust and the Biotechnology and Biological Sciences Research Council (BBSRC), supporting a team that included both cell biologists and biophysicists.
The next stage of this work is to look at a greater number of proteins that form amyloid fibres in order to consolidate these findings, says co-author and cell biologist Dr Eric Hewitt. "What we've discovered is fundamental and offers a whole new area for those working on therapeutics in this area. We anticipate that when we look at amyloid fibres formed from other proteins, they may well follow the same rules."
The team also hopes to discover why the shorter amyloid fibres are more toxic that their longer counterparts.
"It may be that because they're smaller it's easier for them to infiltrate cells," says Dr Hewitt. "We've observed them killing cells, but we're not sure yet exactly how they do it. Nor do we know whether these short fibres form naturally when amyloid fibres assemble or whether some molecular process makes them disassemble or fragment into shorter fibres.These are our next big challenges."
For more information go to: www.parkinsonresearchfoundation.org
It was believed that amyloid fibrils - rope-like structures made up of proteins sometimes known as fibres - are inert, but that there may be toxic phases during their formation which can damage cells and cause disease.
But in a paper published today [04 December 2009] in the Journal of Biological Chemistry, scientists at the University of Leeds have shown that amyloid fibres are in fact toxic - and that the shorter the fibre, the more toxic it becomes.
"This is a major step forward in our understanding of amyloid fibrils which play a role in such a large number of diseases," said Professor Sheena Radford of the Astbury Centre for Structural Molecular Biology and the Faculty of Biological Sciences.
"We've revisited an old suspect with very surprising results. Whilst we've only looked in detail at three of the 30 or so proteins that form amyloid in human disease, our results show that the fibres they produce are indeed toxic to cells especially when they are fragmented into shorter fibres. "
Amyloid deposits can accumulate at many different sites in the body or can remain localised to one particular organ or tissue, causing a range of different diseases. Amyloid deposits can be seen in the brain, in diseases such as Parkinson's and Alzheimer's, whereas in other amyloid diseases deposits can be found elsewhere in the body, in the joints, liver and many other organs. Amyloid deposits are also closely linked to the development of Type II diabetes.
Professor Radford said: "Problems in the self-assembly process that results in the formation of amyloid are a natural consequence of longer life. In fact 85 per cent of all cases of disease caused by amyloid deposits are seen in those over the age of sixty or so."
The study was funded by the Wellcome Trust and the Biotechnology and Biological Sciences Research Council (BBSRC), supporting a team that included both cell biologists and biophysicists.
The next stage of this work is to look at a greater number of proteins that form amyloid fibres in order to consolidate these findings, says co-author and cell biologist Dr Eric Hewitt. "What we've discovered is fundamental and offers a whole new area for those working on therapeutics in this area. We anticipate that when we look at amyloid fibres formed from other proteins, they may well follow the same rules."
The team also hopes to discover why the shorter amyloid fibres are more toxic that their longer counterparts.
"It may be that because they're smaller it's easier for them to infiltrate cells," says Dr Hewitt. "We've observed them killing cells, but we're not sure yet exactly how they do it. Nor do we know whether these short fibres form naturally when amyloid fibres assemble or whether some molecular process makes them disassemble or fragment into shorter fibres.These are our next big challenges."
For more information go to: www.parkinsonresearchfoundation.org
Thursday, December 3, 2009
Stomach Hormone Can Boost Resistance To Or Slow Down Parkinson's
US researchers report finding that ghrelin, a hormone produced in the stomach that regulates appetite and how the body deposits fat, may be used to boost resistance to or slow the development of Parkinson's disease.
The study is the work of Dr Tamas Horvath, chair and professor of comparative medicine and professor of neurobiology and obstetrics and gynecology at the Yale University School of Medicine, New Haven, Connecticut, and colleagues and was published earlier this month in The Journal of Neuroscience.
Parkinson's disease is a neurodegenerative disorder where dopamine neurons in an area of the midbrain known as the substantia nigra, which is responsible for dopamine production, start to die off.
As less dopamine is produced, the symptoms become more severe, so that eventually people with the disease have difficulty walking, have restricted and delayed movements, get tremors in their head and limbs, lose their appetite, can't eat properly, and have periods of immobility or "freezing".
We already know that ghrelin targets the hypothalamus and affects appetite, food intake and how the body deposits fat. The authors wrote that ghrelin receptors at sites outside of the hypothalamus also "promote circuit activity associated with learning and memory, and reward seeking behavior". And recent human studies have shown that body mass index (BMI), stored fat and diabetes are linked to Parkinson's disease.
In this study, Horvath and colleagues discovered that ghrelin also protects the neurons that make dopamine.
"We also found that, in addition to its influence on appetite, ghrelin is responsible for direct activation of the brain's dopamine cells," said Horvath. He explained that because the hormone is made in the stomach, it circulates normally in the bloodstream, "so it could easily be used to boost resistance to Parkinson's or it could be used to slow the development of the disease".
For the study, which was supported by the Michael J Fox Foundation for Parkinson's Research, Horvath and colleagues gave one group of mice extra ghrelin, and while another group were genetically engineered to lack the hormone and its receptor.
When compared to a group of control mice, the mice that had impaired ghrelin action in the brain had more dopamine loss.
The authors explained that the mice that were given extra ghrelin lost fewer substantia nigra pars compacta dopamine cells and showed "restricted striatal dopamine loss", while the mice that were genetically engineered to lack the hormone and its receptors lost more substantia nigra pars compacta dopamine cells and showed "lowered striatal dopamine levels". The effect in the genetically engineered mice was reversed when they switched the ghrelin receptor on.
They concluded that their study supports the idea that ghrelin could be a new therapeutic strategy to fight neurodegeneration, loss of appetite and body weight linked with Parkinson's disease.
Horvath said they could see these results being applicable to humans because the ghrelin system is preserved through various species.
The researchers are now planning to find out how ghrelin levels differ between healthy people and people with Parkinsons disease, and whether changes in ghrelin levels might serve as a biomarker of disease susceptibility and development.
For more information go to www.parkinsonresearchfoundation.org
The study is the work of Dr Tamas Horvath, chair and professor of comparative medicine and professor of neurobiology and obstetrics and gynecology at the Yale University School of Medicine, New Haven, Connecticut, and colleagues and was published earlier this month in The Journal of Neuroscience.
Parkinson's disease is a neurodegenerative disorder where dopamine neurons in an area of the midbrain known as the substantia nigra, which is responsible for dopamine production, start to die off.
As less dopamine is produced, the symptoms become more severe, so that eventually people with the disease have difficulty walking, have restricted and delayed movements, get tremors in their head and limbs, lose their appetite, can't eat properly, and have periods of immobility or "freezing".
We already know that ghrelin targets the hypothalamus and affects appetite, food intake and how the body deposits fat. The authors wrote that ghrelin receptors at sites outside of the hypothalamus also "promote circuit activity associated with learning and memory, and reward seeking behavior". And recent human studies have shown that body mass index (BMI), stored fat and diabetes are linked to Parkinson's disease.
In this study, Horvath and colleagues discovered that ghrelin also protects the neurons that make dopamine.
"We also found that, in addition to its influence on appetite, ghrelin is responsible for direct activation of the brain's dopamine cells," said Horvath. He explained that because the hormone is made in the stomach, it circulates normally in the bloodstream, "so it could easily be used to boost resistance to Parkinson's or it could be used to slow the development of the disease".
For the study, which was supported by the Michael J Fox Foundation for Parkinson's Research, Horvath and colleagues gave one group of mice extra ghrelin, and while another group were genetically engineered to lack the hormone and its receptor.
When compared to a group of control mice, the mice that had impaired ghrelin action in the brain had more dopamine loss.
The authors explained that the mice that were given extra ghrelin lost fewer substantia nigra pars compacta dopamine cells and showed "restricted striatal dopamine loss", while the mice that were genetically engineered to lack the hormone and its receptors lost more substantia nigra pars compacta dopamine cells and showed "lowered striatal dopamine levels". The effect in the genetically engineered mice was reversed when they switched the ghrelin receptor on.
They concluded that their study supports the idea that ghrelin could be a new therapeutic strategy to fight neurodegeneration, loss of appetite and body weight linked with Parkinson's disease.
Horvath said they could see these results being applicable to humans because the ghrelin system is preserved through various species.
The researchers are now planning to find out how ghrelin levels differ between healthy people and people with Parkinsons disease, and whether changes in ghrelin levels might serve as a biomarker of disease susceptibility and development.
For more information go to www.parkinsonresearchfoundation.org
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