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Animal model of Parkinson's disease reveals striking sensitivity to common environmental toxins
September 07, 2005In findings that support a relationship between agricultural chemicals and Parkinson's disease, two groups of researchers have found new evidence that loss of DJ-1, a gene known to be linked to inherited Parkinson's disease, leads to striking sensitivity to the herbicide paraquat and the insecticide rotenone. The two studies were performed with the fruit fly Drosophila, a widely used model organism for studies of human disease, and shed new light on biological connections between inherited and sporadic forms of Parkinson's disease.
The work is reported in Current Biology by two independent groups, one led by Nancy Bonini of the University of Pennsylvania and the Howard Hughes Medical Institute, and the other led by Kyung-Tai Min of the NINDS branch of the U.S. National Institutes of Health.
Parkinson's disease occurs both sporadically and as a result of inheritance of single gene mutations. One of the most common neurodegenerative disorders, it is associated with the progressive and selective loss of a specific population of neurons in the brain, the dopaminergic neurons of the substantia nigra pars compacta . Exposure to several common environmental toxins, thought to injure neurons through oxidative damage, has been shown to be associated with sporadic forms of Parkinson's disease. During the past decade, researchers have also made remarkable progress in identifying genes responsible for inherited forms of Parkinson's disease, with the expectation that understanding the function of these genes will elucidate mechanisms behind sporadic Parkinson's disease. Past work had shown that one form of familial Parkinson's disease results from a loss of function of a gene called DJ-1.
The fruit fly possesses two versions of the DJ-1 gene, and in the new work, the researchers simulated the human Parkinson's disease situation by deleting one or both forms of DJ-1 from the fly's DNA.
Bonini and colleagues showed that flies lacking both forms of DJ-1 activity are normal under standard conditions. However, upon exposure to widely used agricultural agents, including paraquat and rotenone, previously associated with the sporadic form of Parkinson's disease, the flies show strikingly increased sensitivity and death. These findings suggest that loss of DJ-1 function leads to an increased sensitivity to chemical agents that cause oxidative damage.
Min and his colleagues found that loss of function of one form of fly DJ-1, DJ-1b, caused a compensatory boost in expression of the other form of the gene, DJ-1a. These flies, lacking DJ-1â function but having increased DJ-1á activity, showed extended survival of dopaminergic neurons and resistance to oxidative stress caused by the chemical paraquat, but at the same time they also exhibited acute sensitivity to hydrogen peroxide treatment. The results showed that overexpression of DJ-1a in dopaminergic neurons is sufficient to confer protection against paraquat insult.
Together, the results from the two studies suggest that Drosophila DJ-1 genes, and potentially human DJ-1, play critical roles in the survival of dopaminergic neurons and the response to oxidative cellular stress. In addition, the studies also highlight DJ-1 as a potential therapeutic target for the treatment of Parkinson's disease.
Cell Press
The fruit fly possesses two versions of the DJ-1 gene, and in the new work, the researchers simulated the human Parkinson's disease situation by deleting one or both forms of DJ-1 from the fly's DNA.
Bonini and colleagues showed that flies lacking both forms of DJ-1 activity are normal under standard conditions. However, upon exposure to widely used agricultural agents, including paraquat and rotenone, previously associated with the sporadic form of Parkinson's disease, the flies show strikingly increased sensitivity and death. These findings suggest that loss of DJ-1 function leads to an increased sensitivity to chemical agents that cause oxidative damage.
Min and his colleagues found that loss of function of one form of fly DJ-1, DJ-1b, caused a compensatory boost in expression of the other form of the gene, DJ-1a. These flies, lacking DJ-1â function but having increased DJ-1á activity, showed extended survival of dopaminergic neurons and resistance to oxidative stress caused by the chemical paraquat, but at the same time they also exhibited acute sensitivity to hydrogen peroxide treatment. The results showed that overexpression of DJ-1a in dopaminergic neurons is sufficient to confer protection against paraquat insult.
Together, the results from the two studies suggest that Drosophila DJ-1 genes, and potentially human DJ-1, play critical roles in the survival of dopaminergic neurons and the response to oxidative cellular stress. In addition, the studies also highlight DJ-1 as a potential therapeutic target for the treatment of Parkinson's disease.
Cell Press
Parkinsons Disease Current Events and Parkinsons Disease News RSSRutgers Research: Direct Evidence of the Role of Sleep in Memory Formation is Uncovered
A Rutgers University, Newark and Collége de France, Paris research team has pinpointed for the first time the mechanism that takes place during sleep that causes learning and memory formation to occur.
Higher occurrence of Parkinson's linked to low LDL cholesterol
People with low levels of LDL cholesterol are more likely to have Parkinson's disease than people with high LDL levels, according to University of North Carolina at Chapel Hill researchers.
Synchronous neuronal firing may underlie Parkinson's disease
In a finding that contradicts current theories behind Parkinson's disease, neuroscientists at Duke University Medical Center have discovered in mice that critical nerve cells fire all at the same time and thus overwhelm the brain's ability to control the body's movements.
Dopamine imbalances cause sleep disorders in animal models of Parkinson's disease and schizophrenia
Neuroscientists at Duke University Medical Center working with genetically engineered mice have found that the brain chemical dopamine plays a critical role in regulating sleep and brain activity associated with dreaming.
Researchers announce results of study on genetic variation in Parkinson's disease
Researchers at the National Institutes of Health (NIH) have completed one of the first large-scale studies of the role of common genetic variation in Parkinson's disease (PD).
Laser probe of a brain pigment's anatomy may offer insight into Parkinson's disease
In a finding that may offer clues about Parkinson's disease, a team led by Duke University researchers used a sophisticated laser system to gain evidence that a dark brown pigment that accumulates in people's brains consists of layers of two other pigments commonly found in hair.
Two copies of G2019S Parkinson's gene mutation doesn't lead to more severe disease
A group of Parkinson's disease researchers concluded there are no observable differences between those who have two copies of the most common mutation of the recently discovered LRRK2 gene and those who have only one copy.
Government cash injection for University spin-out company's stem cell research
A spin-out company from the University of Nottingham has been awarded around £250,000 of Government funding to develop innovative stem cell therapies that could one day provide new treatments for patients suffering from illnesses including Parkinson's disease and stroke.
Two minutes of magnetic stimulation can change your brain for an hour
A couple of minutes is all it takes to 'knock out' bits of your brain for an hour, according to a new study by a University College London (UCL) team. The team have been working on ways to improve a method known as transcranial magnetic stimulation (TMS) and are now using their adapted version of TMS to investigate possible treatments for stroke patients or those with Parkinson's disease.
Gene therapy shows promise in model of Parkinson's disease
Scientists at the Ecole Polytechnique Federale de Lausanne (EPFL) in Lausanne, Switzerland, have conducted novel experiments that might one day lead to gene therapy treatment options for patients with Parkinson's disease. In research published this week in the Proceedings of the National Academy of Sciences, the research team, led by EPFL President Patrick Aebischer, found that viral delivery of a gene associated with Parkinson's disease protected neurons from degeneration. Parkinson's disease is a progressive, degenerative neurological disorder in which dopamine-producing neurons in the part of the brain responsible for coordinating muscle movement die or become so damaged that they are no
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