Author: Shamim ShaikhLouise Nicholson
Exposure to toxins / chemicals is considered to be a significant risk factor in the pathogenesis of Parkinson's disease (PD); one putative chemical is the naturally occurring herbicide rotenone that is now used widely in establishing PD models. We, and others, have shown that chronic low dose rotenone treatment induces excessive accumulation of Reactive Oxygen Species (ROS), inclusion body formation and apoptosis in dopaminergic neurons of animal and human origin.
Some studies have also suggested that microglia enhance the rotenone induced neurotoxicity. While the effects of rotenone on neurons are well established, there is little or no information available on the effect of rotenone on microglial cells, and especially cells of human origin.
The aim of the present study was to investigate the effects of chronic low dose rotenone treatment on human microglial CHME-5 cells.
Methods: We have shown previously that rotenone induced inclusion body formation in human dopaminergic SH-SY5Y cells and therefore used these cells as a control for inclusion body formation in this study. SH-SY5Y and CHME-5 cells were treated with 5nM rotenone for four weeks.
At the end of week 4, both cell types were analysed for the presence of inclusion bodies, superoxide dismutases and cell activation (only in CHME-5 cells) using Haematoxylin and Eosin staining, immunocytochemical and western blotting methods. Levels of active caspases and ROS (both extra and intra cellular) were measured using biochemical methods.
Conclusion: The results suggest that chronic low dose rotenone treatment activates human microglia (cell line) in a manner similar to microglia of animal origin as shown by others.
However human microglia release excessive amounts of ROS extracellularly, do not show excessive amounts of intracellular ROS and active caspases and most importantly do not show any protein aggregation or inclusion body formation. Human microglia appear to be resistant to rotenone (chronic, low dose) induced damage.
For more information go to www.parkinsonresearchfoundation.org
Monday, January 4, 2010
Sunday, December 27, 2009
University of Iowa Professor to Tackle Dopamine-Reducing Protein
There is a new ray of hope for the one million people who suffer from Parkinson's disease. At the University of Iowa, distinguished professor of biomedical sciences Anumantha Kanthasamy has been working for more than ten years to gain a deeper understanding of Parkinson's disease and its
causes. Now, Dr. Kanthasamy has discovered a protein which could be an important key in the search for a treatment and cure for this debilitating disease.
The protein, called kinase-C, targets the dopamine-producing cells in the brain, killing them and causing a drop in dopamine levels. Low dopamine levels are one of the causes of Parkinson's disease. Dr. Kanthasamy states, "We have millions of cells in our brains. In Parkinson's, about 10,000 of these brain cells die; no one knows why." Dopamine is the link in the communication system between our brains and our muscles. Without dopamine, nerves function improperly and the communication breaks down causing a loss in our ability to control our body's movements.
The level of dopamine in our brains drops gradually as we age. In fact, Dr. Kanthasamy states that "everybody has a little Parkinson's in theory." In any older adult, dopamine levels that drop below 60-70 percent will create some Parkinson's-like symptoms. In adults diagnosed with Parkinson's, the dopamine levels continue to drop well below 40 percent causing a marked increase in symptoms such as shakiness, stiffness, fidgeting and jerking.
Kanthasamy states that a patient suffering from Parkinson's could be a "functioning, normal person," if their dopamine levels could be raised back to the 40-50 percent level. They would not need to bring their dopamine levels back to 100 percent. Currently there is no cure for Parkinson's disease, only therapies and medications to treat the symptoms.
For more information go to www.parkinsonresearchfoundation.org
causes. Now, Dr. Kanthasamy has discovered a protein which could be an important key in the search for a treatment and cure for this debilitating disease.
The protein, called kinase-C, targets the dopamine-producing cells in the brain, killing them and causing a drop in dopamine levels. Low dopamine levels are one of the causes of Parkinson's disease. Dr. Kanthasamy states, "We have millions of cells in our brains. In Parkinson's, about 10,000 of these brain cells die; no one knows why." Dopamine is the link in the communication system between our brains and our muscles. Without dopamine, nerves function improperly and the communication breaks down causing a loss in our ability to control our body's movements.
The level of dopamine in our brains drops gradually as we age. In fact, Dr. Kanthasamy states that "everybody has a little Parkinson's in theory." In any older adult, dopamine levels that drop below 60-70 percent will create some Parkinson's-like symptoms. In adults diagnosed with Parkinson's, the dopamine levels continue to drop well below 40 percent causing a marked increase in symptoms such as shakiness, stiffness, fidgeting and jerking.
Kanthasamy states that a patient suffering from Parkinson's could be a "functioning, normal person," if their dopamine levels could be raised back to the 40-50 percent level. They would not need to bring their dopamine levels back to 100 percent. Currently there is no cure for Parkinson's disease, only therapies and medications to treat the symptoms.
For more information go to www.parkinsonresearchfoundation.org
Sunday, December 13, 2009
Parkinson’s Disease Patients Treated with Autologous Bone Marrow Stem Cells May Improve Their Quality of Life
Eight Parkinson’s Disease patients were treated with their own bone marrow stem cells (BMSC) injected via minimally invasive non-surgical routes and discharged the next morning without complications.
“We show the clinical use of autologous BMSC in PD patients, not in animal tests” leader investigator Dr. Luis Geffner said.
Evaluations with UPDRS, Hoehn & Yahr scale and Schwab & England score showed encouraging improvements such as the graphologic tests performed before and after the trasplant that demonstrated significant differences.
Additionally the total L-dopamine dose could be decreased suggesting that stem cells may enhance endogenous dopamine synthesis. He also explained that they are very cautious and prudent emphasizing that they are not talking about cure but stem cells may possibly be a new tool to complement current treatments and delay the progress either of the illness or its complications such as the side effects of some medication.
This study showing safety and feasibility of autologous adult BMSC transplant in PD patients was presented in Baltimore on October 11th 2009 in the 23rd Annual Symposium of Etiology, Pathogenesis and Treatment of Parkinson’s Disease and other Movement Disorders organized by the Parkinson Study Group in affiliation with the American Neurological Association and published in September 2009 issue of Movement Disorders, a peer -review journal.
Geffner's team has already transplanted 144 patients suffering from different illnesses or trauma states and many of them have been followed up 5 years showing that autologous adult BMSC neither provoke tumors, immunologic rejection, infections nor arise ethical or religious controversies.
Dr. Geffner has been working in the field of clinical application of stem cells since 2001 and is author and co-author of several papers, lecturer in many meetings and has also founded the stem cells research in Ecuador in July 2004.
He is in charge of the Clinical Research & Regenerative Medicine Department of the University Hospital SHDUG of the state University of Guayaquil, Ecuador (www.stemcellsecuador.com).
Programs in various diseases and trauma states are currently being performed by his team and they expect to have new data to publish in the near future.
For more information go to www.parkinsonresearchfoundation.org
“We show the clinical use of autologous BMSC in PD patients, not in animal tests” leader investigator Dr. Luis Geffner said.
Evaluations with UPDRS, Hoehn & Yahr scale and Schwab & England score showed encouraging improvements such as the graphologic tests performed before and after the trasplant that demonstrated significant differences.
Additionally the total L-dopamine dose could be decreased suggesting that stem cells may enhance endogenous dopamine synthesis. He also explained that they are very cautious and prudent emphasizing that they are not talking about cure but stem cells may possibly be a new tool to complement current treatments and delay the progress either of the illness or its complications such as the side effects of some medication.
This study showing safety and feasibility of autologous adult BMSC transplant in PD patients was presented in Baltimore on October 11th 2009 in the 23rd Annual Symposium of Etiology, Pathogenesis and Treatment of Parkinson’s Disease and other Movement Disorders organized by the Parkinson Study Group in affiliation with the American Neurological Association and published in September 2009 issue of Movement Disorders, a peer -review journal.
Geffner's team has already transplanted 144 patients suffering from different illnesses or trauma states and many of them have been followed up 5 years showing that autologous adult BMSC neither provoke tumors, immunologic rejection, infections nor arise ethical or religious controversies.
Dr. Geffner has been working in the field of clinical application of stem cells since 2001 and is author and co-author of several papers, lecturer in many meetings and has also founded the stem cells research in Ecuador in July 2004.
He is in charge of the Clinical Research & Regenerative Medicine Department of the University Hospital SHDUG of the state University of Guayaquil, Ecuador (www.stemcellsecuador.com).
Programs in various diseases and trauma states are currently being performed by his team and they expect to have new data to publish in the near future.
For more information go to www.parkinsonresearchfoundation.org
Thursday, December 3, 2009
Ghrelin hormone "can boost resistance" to Parkinson's
Ghrelin can boost a person's resistance to Parkinson's disease, it has been discovered.
The importance of dopamine in regards to Parkinson's disease has been addressed by researchers in the US.
It is a widely-held understanding that the degeneration of dopamine neurons in an area of the brain known as the substantia nigra - which is responsible for dopamine production - leads to a worsening of conditions.
This can lead to an increased difficulty in walking, restricted movements, a lack of appetite, periods of motionlessness and notable head and limb tremors, according to scientists on the project at the Yale School of Medicine.
Tamas Horvath, the chair of the facility and professor of comparative medicine, explained that he and his team discovered that ghrelin is responsible for directly activating the brain's dopamine calls.
He continued: "Because this hormone originates from the stomach, it is circulating normally in the body, so it could easily be used to boost resistance to Parkinson's or it could be used to slow the development of the disease."
Earlier this month, it was discovered that red tomatoes contain a lot of ghrelin, as well as making a person feel fuller quicker.
For more information go to www.parkinsonresearchfoundation.org
The importance of dopamine in regards to Parkinson's disease has been addressed by researchers in the US.
It is a widely-held understanding that the degeneration of dopamine neurons in an area of the brain known as the substantia nigra - which is responsible for dopamine production - leads to a worsening of conditions.
This can lead to an increased difficulty in walking, restricted movements, a lack of appetite, periods of motionlessness and notable head and limb tremors, according to scientists on the project at the Yale School of Medicine.
Tamas Horvath, the chair of the facility and professor of comparative medicine, explained that he and his team discovered that ghrelin is responsible for directly activating the brain's dopamine calls.
He continued: "Because this hormone originates from the stomach, it is circulating normally in the body, so it could easily be used to boost resistance to Parkinson's or it could be used to slow the development of the disease."
Earlier this month, it was discovered that red tomatoes contain a lot of ghrelin, as well as making a person feel fuller quicker.
For more information go to www.parkinsonresearchfoundation.org
Monday, November 23, 2009
Parkinson's breakthrough brings treatment hope
Australian scientists researching the causes of Parkinson's disease say their breakthrough will help develop new ways of treating other debilitating illnesses.
Neuroscientists at the Garvan Institute in Sydney have discovered how the brain's dopamine nerve cells regulate the release of the hormone to control the body's movements.
The debilitating shaking symptoms of Parkinson's happen when the brain does not produce enough of the substance.
Dr Bryce Vissel says it is a big step forward in treating the disease.
"We're going to be using this method to actually discover how drugs treat Parkinson's disease currently and to make new therapeutic developments that may be completely novel, completely new ways of treating Parkinson's," he said.
Dr James Daniel says the discovery will help develop new drugs to treat the rising number of sufferers, but it also has wider implications.
"We're talking a lot about Parkinson's disease because that's been the primary focus of our research but these cells are also very important in a number of other neurological disorders," he said.
"They're critically implicated in schizophrenia - the model system can be applied exactly the same way to studying that."
For more information go to www.parkinsonresearchfoundation.org
Neuroscientists at the Garvan Institute in Sydney have discovered how the brain's dopamine nerve cells regulate the release of the hormone to control the body's movements.
The debilitating shaking symptoms of Parkinson's happen when the brain does not produce enough of the substance.
Dr Bryce Vissel says it is a big step forward in treating the disease.
"We're going to be using this method to actually discover how drugs treat Parkinson's disease currently and to make new therapeutic developments that may be completely novel, completely new ways of treating Parkinson's," he said.
Dr James Daniel says the discovery will help develop new drugs to treat the rising number of sufferers, but it also has wider implications.
"We're talking a lot about Parkinson's disease because that's been the primary focus of our research but these cells are also very important in a number of other neurological disorders," he said.
"They're critically implicated in schizophrenia - the model system can be applied exactly the same way to studying that."
For more information go to www.parkinsonresearchfoundation.org
Friday, November 13, 2009
Brain Imaging of Early Stage Parkinson’s
By Rick Nauert PhD
A research team from the University of Illinois at Chicago plans to use cutting-edge technology to study early-stage Parkinson’s disease.
They hope that tests using functional and high-resolution structural brain imaging will reveal new clues about early Parkinson’s disease.
Parkinson’s disease is a progressive, debilitating movement disorder pharmaceutically managed by using drugs that compensate for a lack of the neurotransmitter dopamine. Parkinson’s patients have a deficit of this important chemical because of degeneration in an area of the brain stem where it is made — a structure called the substantia nigra.
The National Institutes of Health has awarded David Vaillancourt and his team a two-year, $855,000 grant to do the work.
“What’s not well understood is how the structure and function of the basal ganglia, or other parts of the brain, are affected early on in the disease,” said Vaillancourt.
He and his colleagues will recruit 25 subjects with early signs of Parkinson’s who haven’t yet begun taking drugs to control the disease. Their study will compare findings to a control group matched for age, gender and handedness — because all subjects will perform motor tasks with their hands while their brain is being imaged.
The study will be the first into early Parkinson’s to use functional brain imaging during gripping tasks designed to simulate everyday activities such as buttoning a shirt or blouse, or holding a cup.
“Individuals will undergo a brain scan while they exert force using their hands against a device that measures how hard and how fast they squeeze,” said Vaillancourt.
“Functional brain imaging will be targeted at the basal ganglia, which is the part of the brain that underlies symptoms of Parkinson’s disease.”
Vaillancourt’s group wants to study what is happening before Parkinson’s patients begin treatment with drugs such as levodopa that can change the way the brain functions. Pretreatment brain scans may be useful to develop markers for screening and diagnosis.
Those with Parkinson’s will be imaged as soon as possible after volunteering and will begin treatment with anti-Parkinson’s drugs afterward.
“With Parkinson’s, the brain must change over time, because it’s a neurodegenerative disease,” Vaillancourt said.
“This study will serve as the basis for trying to understand how the disease progresses.”
For more information go to www.parkinsonresearchfoundation.org
A research team from the University of Illinois at Chicago plans to use cutting-edge technology to study early-stage Parkinson’s disease.
They hope that tests using functional and high-resolution structural brain imaging will reveal new clues about early Parkinson’s disease.
Parkinson’s disease is a progressive, debilitating movement disorder pharmaceutically managed by using drugs that compensate for a lack of the neurotransmitter dopamine. Parkinson’s patients have a deficit of this important chemical because of degeneration in an area of the brain stem where it is made — a structure called the substantia nigra.
The National Institutes of Health has awarded David Vaillancourt and his team a two-year, $855,000 grant to do the work.
“What’s not well understood is how the structure and function of the basal ganglia, or other parts of the brain, are affected early on in the disease,” said Vaillancourt.
He and his colleagues will recruit 25 subjects with early signs of Parkinson’s who haven’t yet begun taking drugs to control the disease. Their study will compare findings to a control group matched for age, gender and handedness — because all subjects will perform motor tasks with their hands while their brain is being imaged.
The study will be the first into early Parkinson’s to use functional brain imaging during gripping tasks designed to simulate everyday activities such as buttoning a shirt or blouse, or holding a cup.
“Individuals will undergo a brain scan while they exert force using their hands against a device that measures how hard and how fast they squeeze,” said Vaillancourt.
“Functional brain imaging will be targeted at the basal ganglia, which is the part of the brain that underlies symptoms of Parkinson’s disease.”
Vaillancourt’s group wants to study what is happening before Parkinson’s patients begin treatment with drugs such as levodopa that can change the way the brain functions. Pretreatment brain scans may be useful to develop markers for screening and diagnosis.
Those with Parkinson’s will be imaged as soon as possible after volunteering and will begin treatment with anti-Parkinson’s drugs afterward.
“With Parkinson’s, the brain must change over time, because it’s a neurodegenerative disease,” Vaillancourt said.
“This study will serve as the basis for trying to understand how the disease progresses.”
For more information go to www.parkinsonresearchfoundation.org
Wednesday, November 4, 2009
Cholesterol-lowering drug could prevent Parkinson's
A commonly used cholesterol-lowering drug, called Simvastatin, can prevent progression of Parkinson's disease, according to a study by neurological Cholesterol-lowering drug could prevent Parkinson's researchers at Rush University Medical Center .
The study examined the use of the FDA-approved medication in mice with Parkinson’s disease and found that the drug successfully reverses the biochemical, cellular and anatomical changes caused by the disease.
"Statins are one of the most widely used cholesterol-lowering drugs throughout the world. This may be a safer approach to halt the disease progression in Parkinson’s patients," said study author Dr. Kalipada Pahan.
The researchers have shown that the activity of one protein called p21Ras is increased very early in the midbrain of mice with Parkinson’s pathology.
Simvastatin enters into the brain and blocks the activity of the p21Ras protein and other associated toxic molecules, and goes on to protect the neurons, normalize neurotransmitter levels, and improves the motor functions in the mice with Parkinson’s.
"Understanding how the disease works is important to developing effective drugs that protect the brain and stop the progression of Parkinson’s. If we are able to replicate these results in Parkinson’s patients in the clinical setting, it would be a remarkable advance in the treatment of this devastating neurodegenerative disease," said Pahan.
For more information go to www.parkinsonresearchfoundation.org
The study examined the use of the FDA-approved medication in mice with Parkinson’s disease and found that the drug successfully reverses the biochemical, cellular and anatomical changes caused by the disease.
"Statins are one of the most widely used cholesterol-lowering drugs throughout the world. This may be a safer approach to halt the disease progression in Parkinson’s patients," said study author Dr. Kalipada Pahan.
The researchers have shown that the activity of one protein called p21Ras is increased very early in the midbrain of mice with Parkinson’s pathology.
Simvastatin enters into the brain and blocks the activity of the p21Ras protein and other associated toxic molecules, and goes on to protect the neurons, normalize neurotransmitter levels, and improves the motor functions in the mice with Parkinson’s.
"Understanding how the disease works is important to developing effective drugs that protect the brain and stop the progression of Parkinson’s. If we are able to replicate these results in Parkinson’s patients in the clinical setting, it would be a remarkable advance in the treatment of this devastating neurodegenerative disease," said Pahan.
For more information go to www.parkinsonresearchfoundation.org
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