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New genetic model for Parkinson's disease
July 28, 2006Researchers at the Karolinska Institute in Sweden are homing in on mechanisms that may explain one set of causes for Parkinson's disease. In mice they have mimicked disturbances of mitochondria thought to be one cause of disease. By genetic means the disturbance of mitochondria-the energy factories of cells-were directed to those nerve cells that produce the transmitter substance dopamine and that die in Parkinson's disease.
"The course of disease in these mice is strikingly similar to human disease", says Dr. Lars Olson.
In the mouse model generated by the research team, a gene called TFAM is automatically deleted from the genome in dopamine nerve cells only. Without TFAM, mitochondria cannot function normally. The so called respiratory chain is compromised and energy production decreases severely in the dopamine cells.
The new mice are born healthy from healthy but genetically modified parents and will develop spontaneous disease. Previous studies in the field have been based on researchers delivering neurotoxic substances to kill the dopamine neurons. In the new mice, however, mice develop disease slowly in adulthood, like humans with Parkinson's disease, which may facilitate research aimed at finding novel medical treatments and other therapies.
"We see that the dopamine producing nerve cells in the brain stem slowly degenerate", says Dr. Nils-Göran Larsson. "In the microscope we can see that the mitochondria are swollen and that aggregates of a protein, probably alpha-synuclein starts to accumulate in the nerve cell bodies. Inclusions of alpha-synuclein-rich so called Lewy bodies is typical for the human disease."
The causes of Parkinson's disease have long remained a mystery. Genes and environment are both implicated, but recently there has been an increased focus on the roles of genetic factors. It has been found that mutations in a number of genes can lead directly to disease, while other mutations may be susceptibility factors, so that carriers have an increased risk of becoming ill. A common denominator for some of the implicated genes is their suggested role for the normal functioning of mitochondria.
"Like patients, the mice can be treated with levo-Dopa, a precursor of the lost substance dopamine", says Dr. Nils-Göran Larsson. "The course of the disease as well as the brain changes in this mouse are more similar to Parkinson's disease than most other models. This supports the notion that genetic risk factors are important."
"Like in patients, the dopamine nerve cells in the new mouse model die in a specific order", says Dr. Lars Olson. "We hope the mouse will help us understand why certain dopamine nerve cells are more sensitive than others, so that we can develop drugs that delay, ore even stop the nerve cell death."
Karolinska Institutet
The new mice are born healthy from healthy but genetically modified parents and will develop spontaneous disease. Previous studies in the field have been based on researchers delivering neurotoxic substances to kill the dopamine neurons. In the new mice, however, mice develop disease slowly in adulthood, like humans with Parkinson's disease, which may facilitate research aimed at finding novel medical treatments and other therapies.
"We see that the dopamine producing nerve cells in the brain stem slowly degenerate", says Dr. Nils-Göran Larsson. "In the microscope we can see that the mitochondria are swollen and that aggregates of a protein, probably alpha-synuclein starts to accumulate in the nerve cell bodies. Inclusions of alpha-synuclein-rich so called Lewy bodies is typical for the human disease."
The causes of Parkinson's disease have long remained a mystery. Genes and environment are both implicated, but recently there has been an increased focus on the roles of genetic factors. It has been found that mutations in a number of genes can lead directly to disease, while other mutations may be susceptibility factors, so that carriers have an increased risk of becoming ill. A common denominator for some of the implicated genes is their suggested role for the normal functioning of mitochondria.
"Like patients, the mice can be treated with levo-Dopa, a precursor of the lost substance dopamine", says Dr. Nils-Göran Larsson. "The course of the disease as well as the brain changes in this mouse are more similar to Parkinson's disease than most other models. This supports the notion that genetic risk factors are important."
"Like in patients, the dopamine nerve cells in the new mouse model die in a specific order", says Dr. Lars Olson. "We hope the mouse will help us understand why certain dopamine nerve cells are more sensitive than others, so that we can develop drugs that delay, ore even stop the nerve cell death."
Karolinska Institutet
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Researchers announce results of study on genetic variation in Parkinson's disease
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Laser probe of a brain pigment's anatomy may offer insight into Parkinson's disease
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Two copies of G2019S Parkinson's gene mutation doesn't lead to more severe disease
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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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