Parkinson disease, how disturb your body

Parkinson's disease also known as paralysis is often defined as a parkinsonian syndrome that is idiopathic although some atypical cases have a genetic origin. It may harm your nervous system.

Parkinson's disease is the most common form of parkinsonism and is usually defined as "primary" parkinsonism, that means parkinsonism with no external identifiable cause. According to our research several genes that are directly related to some cases of Parkinson's disease have been discovered. However, as much as this conflicts with the definition of Parkinson's disease as an idiopathic illness, it is generally assumed that genetic parkinsonism disorders with a similar clinical course to PD are generally included under the Parkinson's disease label.

Parkinson's disease belongs to a group of conditions called motor system disorders that are the result of the loss of dopamine-producing brain cells. Main four primary symptoms of PD are tremor, rigidity or stiffness of the limbs; bradykinesia and postural instability, or impaired coordination and balance. As these symptoms become more difficult, patients may have difficulty talking or walking, or completing other simple tasks. This disease usually affects people over the age of 60.

 According to our research at early symptoms of Parkinson's disease are subtle and occur subsequently.  In some people the disease progresses more quickly than in others when the disease progresses, tremor, which affects the majority of people with Parkinson's disease may begin to interfere with daily activities.  Another symptoms may include depression and other emotional changes; chewing, and speaking; constipation or urinary problems and sleep disruptions. 

There are currently no blood or laboratory tests that have been proven to help in diagnosing sporadic Parkinson's disease.  So, the diagnosis is based on medical history and a neurological examination. . 

Fight against Parkinson disease

Parkinson's disease is a progressive disorder of the nervous system that affects your movement. Though it developes gradually but sometimes starting with a barely noticeable tremor in just one hand.

Parkinson's disease is a progressive disorder of the nervous system that affects your movement. This disease is a movement disorder that progresses slowly. People will first notice a sense of weakness or difficulty walking and stiff muscles. However, others may notice a tremor of the head or hands. Its a progressive disorder and the symptoms gradually worsen. Although Parkinson's disease can't be cured, regular medications may markedly improve your symptoms. Exceptional cases, your doctor may suggest surgery to regulate certain regions of your brain and improve your symptoms.

Parkinson's disease is often defined as a parkinsonian syndrome that is idiopathic i.e. it has no known cause. According to our research, many risks and protective factors have been investigated, however,  the clearest evidence is for an increased risk of PD in people exposed to certain pesticides and a reduced risk in tobacco smokers. As a result of our research it has noticed that the pathology of the disease is characterized by the accumulation of a protein called alpha-synuclein into inclusions called Lewy bodies in neurons, and from insufficient formation and activity of dopamine produced in certain neurons within parts of the midbrain.

Our researchers as noticed that Lewy bodies are the pathological hallmark of the idiopathic disorder and distribution of the Lewy bodies throughout the Parkinsonian brain varies from one individual to another. However, the anatomical distribution of the Lewy bodies is often directly related to the expression and degree of the clinical symptoms of each individual. In typical cases diagnosis is mainly based on symptoms with tests such as neuroimaging being used for confirmation.

Effects of Parkinson disease in your body

Parkinson’s disease affects the nerve cells in the brain that produce dopamine. Symptoms include muscle rigidity or tremors and changes in speech and gait. Treatments can help relieve symptoms though there is no cure.

Parkinson’s disease is a movement disorder that progresses slowly. People will first notice a sense of weakness or difficulty in walking and stiff muscles but others may notice a tremor of the head or hands. This disease is a progressive disorder and the symptoms gradually worsen. Basically this disease is a progressive disorder of the nervous system that affects your movement. Gradually it develops and sometimes starting with a barely noticeable tremor in just one hand. However, while a tremor may be the most well-known sign of Parkinson's disease, disorder also commonly causes stiffness or slowing of movement.

According to our research, in the early stages of Parkinson's disease, patient’s face may show little or no expression or his/her arms may not swing when you walk. His or her speech may become soft or slurred. The disease symptoms worsen as your condition progresses over time. Our team of researchers notices that although Parkinson's disease can't be cured, extensive medications may markedly improve your symptoms. But sometimes, your doctor may suggest surgery to regulate certain regions of your brain and improve your symptoms.

As a result of our research at it is found that Parkinson's disease symptoms and signs may vary from person to person. At first signs may be mild and may go unnoticed. Often symptoms begin on one side of your body and usually remain worse on that side, even after symptoms begin to affect both sides.

Parkinson's signs and symptoms may include- slowed movement, rigid muscles, Tremor, Loss of automatic movements..

Tango dancing benefits to Parkinson's

The study looked at whether a social and physical activity linked to music, such as tango, could have possible therapeutic value for PD patients who characteristically suffer from motor dysfunctions — tremor, rigidity, gait dysfunction — as well as from non-motor symptoms, such as depression, fatigue and cognitive degeneration. Forty men and women with idiopathic Parkinson's disease participated in the study, which involved studio classes with two professional dance teachers. Patients were from the Movement Disorders Clinics of the McGill University Health Centre.
"There's accumulating evidence that habitual physical activity is associated with a lower risk of developing PD, which suggests a potential slowing of PD progression," says Dr. Silvia Rios Romenets, lead researcher in the study with a special interest in Parkinson's disease and dance therapy. Dr. Rios Romenets is a clinical research fellow at the Movement Disorders Clinics at The Neuro and Montreal General Hospital. "In the study, we found the tango was helpful in significantly improving balance and functional mobility, and seemed to encourage patients to appreciate their general course of therapy. We also found modest benefits in terms of patients' cognitive functions and in reducing fatigue. No significant changes were detected in overall motor functions."
Argentine tango may be particularly helpful for improving balance and functional mobility in patients with PD. Tango requires specific steps that involve rhythmically walking forward and backward. This may be particularly helpful for walking difficulties especially for freezing of gait and to prevent backward falls. In addition, tango requires working memory, control of attention, and multitasking to incorporate newly learned and previously learned dance elements, to stay in rhythm with the music, and maneuver around others on the dance floor.
Many PD patients find traditional exercise programs unappealing. Over half of PD patients fail to get their recommended daily dose of physical activity. There is however, a connection between music and the dopamine systems in the brain — which are pivotal for establishing and maintaining behavior. So, combining music with exercise in dance such as the tango, can increase accessibility, enjoyability, and motivation, as well as improving mood and stimulating cognition. Also, the social interaction and social support involved in tango have positive results on mood and compliance.

Journal Referance:
  1. Silvia Rios Romenets, Julius Anang, Seyed-Mohammad Fereshtehnejad, Amelie Pelletier, Ronald Postuma. Tango for treatment of motor and non-motor manifestations in Parkinson's disease: A randomized control study. Complementary Therapies in Medicine, 2015; 23 (2): 175 DOI: 10.1016/j.ctim.2015.01.015

Researchers even closer to early detection of Parkinson's disease

In collaboration with colleagues at Oxford, a team of researchers at Umeå University in Sweden has now further elaborated its discovery of a way to detect Parkinson's disease at an early stage, and applications in clinical care are not far away.

The project is an example of bridging the gap between basic and clinical research in care environments. The new findings are based on close cooperation between the medical chemist Ludmilla Morozova-Roche's and the neurologist Lars Forsgren's research teams at Umeå University and Jason Davis's team at Oxford University in the UK, who were primarily responsible for the chemical analyses. Their findings are now being published in the journal Chemical Science.

Parkinson's disease attacks the nervous system and, like many other diseases, is caused by proteins that lump together into so-called amyloid. Behind these new findings lies a discovery from the spring of 2011, when the Umeå scientists were able to determine endogenous antibodies against the most important amyloid protein, alpha-synuclein. These antibodies were seen as being able to function as a diagnostic marker, thereby enabling early detection of the disease.

In the new article the discovery is elaborated further in the form of a simplified way to carefully measure the content of antibodies in a blood sample. With the newly developed method — this involves electrochemical analysis of 10 microliters of blood in just a few minutes — it is possible not only to see a clear difference between individuals with incipient Parkinson's disease and healthy controls but also to measure and establish the advance of the disease with great precision.

Journal Reference:

  1. Thomas Bryan, Xiliang Luo, Lars Forsgren, Ludmilla A. Morozova-Roche, Jason J. Davis. The robust electrochemical detection of a Parkinson's disease marker in whole blood sera. Chemical Science, 2012; DOI: 10.1039/c2sc21221h

Mechanism that leads to sporadic Parkinson's disease identified

Researchers in the Taub Institute at Columbia University Medical Center (CUMC) have identified a mechanism that appears to underlie the common sporadic (non-familial) form of Parkinson's disease, the progressive movement disorder. The discovery highlights potential new therapeutic targets for Parkinson's and could lead to a blood test for the disease. The study, based mainly on analysis of human brain tissue, was published September 25 in the online edition of Nature Communications.

Studies of rare, familial (heritable) forms of Parkinson's show that a protein called alpha-synuclein plays a role in the development of the disease. People who have extra copies of the alpha-synuclein gene produce excess alpha-synuclein protein, which can damage neurons. The effect is most pronounced in dopamine neurons, a population of brain cells in the substantia nigra that plays a key role in controlling normal movement and is lost in Parkinson's. Another key feature of Parkinson's is the presence of excess alpha-synuclein aggregates in the brain.

As the vast majority of patients with Parkinson's do not carry rare familial mutations, a key question has been why these individuals with common sporadic Parkinson's nonetheless acquire excess alpha-synuclein protein and lose critical dopamine neurons, leading to the disease.

Using a variety of techniques, including gene-expression analysis and gene-network mapping, the CUMC researchers discovered how common forms of alpha-synuclein contribute to sporadic Parkinson's. "It turns out multiple different alpha-synuclein transcript forms are generated during the initial step in making the disease protein; our study implicates the longer transcript forms as the major culprits," said study leader Asa Abeliovich, MD, PhD, associate professor of pathology and neurology at CUMC. "Some very common genetic variants in the alpha-synuclein gene, present in many people, are known to impact the likelihood that an individual will suffer from sporadic Parkinson's. In our study, we show that people with 'bad' variants of the gene make more of the elongated alpha-synuclein transcript forms. This ultimately means that more of the disease protein is made and may accumulate in the brain."

"An unusual aspect of our study is that it is based largely on detailed analysis of actual patient tissue, rather than solely on animal models," said Dr. Abeliovich. "In fact, the longer forms of alpha-synuclein are human-specific, as are the disease-associated genetic variants. Animal models don't really get Parkinson's, which underscores the importance of including the analysis of human brain tissue."

"Furthermore, we found that exposure to toxins associated with Parkinson's can increase the abundance of this longer transcript form of alpha-synuclein. Thus, this mechanism may represent a common pathway by which environmental and genetic factors impact the disease," said Dr. Abeliovich.

The findings suggest that drugs that reduce the accumulation of elongated alpha-synuclein transcripts in the brain might have therapeutic value in the treatment of Parkinson's. The CUMC team is currently searching for drug candidates and has identified several possibilities.

The study also found elevated levels of the alpha-synuclein elongated transcripts in the blood of a group of patients with sporadic Parkinson's, compared with unaffected controls. This would suggest that a test for alpha-synuclein may serve as a biomarker for the disease. "There is a tremendous need for a biomarker for Parkinson's, which now can be diagnosed only on the basis of clinical symptoms. The finding is particularly intriguing, but needs to be validated in additional patient groups," said Dr. Abeliovich. A biomarker could also speed clinical trials by giving researchers a more timely measure of a drug's effectiveness.

The study was supported by the grants from the Michael J. Fox Foundation, the National Institutes of Health, and the National Institute of Neurological Disorders and Stroke (RO1NS064433).

Journal Reference:

  1. Herve Rhinn, Liang Qiang, Toru Yamashita, David Rhee, Ari Zolin, William Vanti, Asa Abeliovich. Alternative α-synuclein transcript usage as a convergent mechanism in Parkinson's disease pathology. Nature Communications, 2012; 3: 1084 DOI: 10.1038/ncomms2032

Key player in Parkinson's disease neuron loss pinpointed

— By reprogramming skin cells from Parkinson's disease patients with a known genetic mutation, researchers at the Salk Institute for Biological Studies have identified damage to neural stem cells as a powerful player in the disease. The findings, reported online October 17th in Nature, may lead to new ways to diagnose and treat the disease.

The scientists found that a common mutation to a gene that produce the enzyme LRRK2, which is responsible for both familial and sporadic cases of Parkinson's disease, deforms the membrane surrounding the nucleus of a neural stem cell. Damaging the nuclear architecture leads to destruction of these powerful cells, as well as their decreased ability to spawn functional neurons, such as the ones that respond to dopamine.

The researchers checked their laboratory findings with brain samples from Parkinson's disease patients and found the same nuclear envelope impairment.

"This discovery helps explain how Parkinson's disease, which has been traditionally associated with loss of neurons that produce dopamine and subsequent motor impairment, could lead to locomotor dysfunction and other common non-motor manifestations, such as depression and anxiety," says Juan Carlos Izpisua Belmonte, a professor in Salk's Gene Expression Laboratory, who led the research team. "Similarly, current clinical trials explore the possibility of neural stem cell transplantation to compensate for dopamine deficits. Our work provides the platform for similar trials by using patient-specific corrected cells. It identifies degeneration of the nucleus as a previously unknown player in Parkinson's."

Although the researchers say that they don't yet know whether these nuclear aberrations cause Parkinson's disease or are a consequence of it, they say the discovery could offer clues about potential new therapeutic approaches.

For example, they were able to use targeted gene-editing technologies to correct the mutation in patient's nuclear stem cells. This genetic correction repaired the disorganization of the nuclear envelope, and improved overall survival and functioning of the neural stem cells.

They were also able to chemically inhibit damage to the nucleus, producing the same results seen with genetic correction. "This opens the door for drug treatment of Parkinson's disease patients who have this genetic mutation," says Belmonte.

The new finding may also help clinicians better diagnose this form of Parkinson's disease, he adds. "Due to the striking appearance in patient samples, nuclear deformation parameters could add to the pool of diagnostic features for Parkinson's disease," he says.

The research team, which included scientists from China, Spain, and the University of California, San Diego, and Scripps Research Institute, made their discoveries using human induced pluripotent stem cells (iPSCs). These cells are similar to natural stem cells, such as embryonic stem cells, except that they are derived from adult cells. While generation of these cells has raised expectations within the biomedical community due to their transplant potential — the idea that they could morph into tissue that needs to be replaced — they also provide exceptional research opportunities, says Belmonte.

"We can model disease using these cells in ways that are not possible using traditional research methods, such as established cell lines, primary cultures and animal models," he says.

In this study, the researchers used skin fibroblast cells taken from Parkinson's disease patients who have the LRRK2 mutation, and they reprogrammed them to iPSC stem cells and developed them into neural stem cells.

Then, by using an approach to model what happens when these neural stem cells aged, they found that older Parkinson disease neural stem cells increasingly displayed deformed nuclear envelopes and nuclear architecture. "This means that, over time, the LRRK2 mutation affects the nucleus of neural stem cells, hampering both their survival and their ability to produce neurons," Belmonte says.

"It is the first time to our knowledge that human neural stem cells have been shown to be affected during Parkinson's pathology due to aberrant LRRK2," he says. "Before development of these reprogramming technologies, studies on human neural stem cells were elusive because they needed to be isolated directly from the brain."

Belmonte speculates that the dysfunctional neural stem cell pools that result from the LRRK2 mutation might contribute to other health issues associated with this form of Parkinson's disease, such as depression, anxiety and the inability to detect smells.

Finally, the study shows that these reprogramming technologies are very useful for modeling disease as well as dysfunction caused by aging, Belmonte says.

The research was supported by Glenn Foundation for Medical Research, G. Harold and Leila Y. Mathers Charitable Foundation, Sanofi, The California Institute of Regenerative Medicine, Ellison Medical Foundation and Leona M. and Harry B. Helmsley Charitable Trust, MINECO and Fundacion Cellex.


Journal Reference:

  1. Guang-Hui Liu, Jing Qu, Keiichiro Suzuki, Emmanuel Nivet, Mo Li, Nuria Montserrat, Fei Yi, Xiuling Xu, Sergio Ruiz, Weiqi Zhang, Ulrich Wagner, Audrey Kim, Bing Ren, Ying Li, April Goebl, Jessica Kim, Rupa Devi Soligalla, Ilir Dubova, James Thompson, John Yates III, Concepcion Rodriguez Esteban, Ignacio Sancho-Martinez, Juan Carlos Izpisua Belmonte. Progressive degeneration of human neural stem cells caused by pathogenic LRRK2. Nature, 2012; DOI: 10.1038/nature11557

Deep brain stimulation changes rhythms to treat Parkinson's disease and tremor

Deep-brain stimulation (DBS) may stop uncontrollable shaking in patients with Parkinson's disease and essential tremor by imposing its own rhythm on the brain, according to two studies published recently by University of Alabama at Birmingham researchers in the journal Movement Disorders. An article addressing brain stimulation for essential tremor was published online August 28; a related article on Parkinson's disease was released May 30.

DBS uses an electrode implanted beneath the skin to deliver electrical pulses into the brain more than 100 times per second. Although this technology was approved by the Food and Drug Administration more than 15 years ago, it remains unclear how it reduces tremor and other symptoms of movement disorders.

With the help of electroencephalography or EEG — electrodes placed on the scalp — study authors used new techniques to suppress the electrical signal associated with the DBS electrode. That enabled the first clear, non-invasive EEG measurements of the underlying brain response during clinically effective, high-frequency brain stimulation in humans.

The results show that nerves in the cerebral cortex, the outer layer of the brain, fire with rapid and precise timing in response to individual stimulus pulses. This suggests that DBS may synchronize the firing of nerve cells and break the abnormal rhythms associated with involuntary movements in Parkinson's disease and essential tremor.

The newly identified rhythm was captured during effective DBS treatment, so it could represent a new physiological measure of the stimulation dose, say the authors. If validated, such a yardstick could help to guide the fine-tuning of DBS stimulator settings in patients for more lasting relief, fewer side effects and less-frequent battery-replacement surgeries.

"Though it's clear that more work is needed to better understand these initial observations, we're very excited by our findings because they may provide a biological marker for improvement in the symptoms of these patients," says Harrison Walker, M.D., assistant professor in the UAB Department of Neurology's Division of Movement Disorders and lead author of the study.

In current clinical practice, stimulator settings are adjusted by trial and error, requiring careful observation of changes in symptoms over multiple clinic visits. But such immediate, visual feedback may not be available as DBS is applied to neurological or psychiatric conditions such as epilepsy, severe depression or obsessive compulsive disorder. In these diseases, an effective dose measurement could be especially useful in optimizing DBS therapy.

A peak emerges

In both studies, EEG data revealed that nerve cells in the cerebral cortex discharged about one one-thousandth of a second, or one millisecond, after each stimulus pulse was delivered into the brain.

The authors argue that this rapid response on the brain's surface most likely represented "backfiring" along extensions of cortical nerve cells called axons that connect them to deeper regions within the brain where the DBS electrodes were placed. Interestingly, this rapid response on the brain surface was present in both studies, regardless of the stimulation target or the disease state of the patient.

Although prior studies had hinted at these brain responses, they were unable to measure them directly because of interference from the competing electrical signal emitted by the DBS pulse itself. Walker and his team reversed the polarity of the stimulation pulse, in effect subtracting the DBS signal and leaving only the EEG signal associated with the brain activity.

The new technique also enabled the researchers to show that the size of the brain response at one millisecond after a DBS pulse is dependent on the intensity or voltage of the stimulus pulse, and that larger brain responses were closely associated with improvement in tremor.

Along with Walker, study authors within the UAB Department of Neurology included He Huang, Christopher Gonzalez, James Bryant and Jeffrey Killen, along with Robert Knowlton, M.D. (now at the University of Texas at Houston Medical Center), Erwin Montgomery Jr., M.D., and Ray Watts, M.D., dean of the UAB School of Medicine. Additional contributions were made by Gary R. Cutter, Ph.D., in the UAB Department of Biostatistics in the School of Public Health, and Barton Guthrie, M.D., in the Division of Neurosurgery. The study was funded by the National Institute of Neurological Disorders and Stroke, part of the U.S. National Institutes of Health.

"While early, this work has tremendous implications for the understanding of brain mechanisms responsible for a number of neurological and psychiatric diseases," says Guthrie. "Further studies are planned to confirm these measures and mechanisms and we believe this insight will soon make valuable contributions to the next generation of DBS treatments."

Journal Reference:

  1. Harrison C. Walker, He Huang, Christopher L. Gonzalez, James E. Bryant, Jeffrey Killen, Robert C. Knowlton, Erwin B. Montgomery, Gary C. Cutter, Abidin Yildirim, Bart L. Guthrie, Ray L. Watts. Short latency activation of cortex by clinically effective thalamic brain stimulation for tremor. Movement Disorders, 2012; DOI: 10.1002/mds.25137

Study examines association between Parkinson disease, cancer

A study that used a Utahgenealogic database and a statewide cancer registry to examine the relationship between Parkinson disease (PD) and cancer suggests an increased risk of prostate cancer and melanoma in patients with PD and their relatives, according to a report published Online First by Archives of Neurology, a JAMA Network publication.

Neurodegenerative diseases, in particular PD, may share common pathogenic mechanisms with some cancers, according to the study background.

"Identifying a genetic relationship between PD and cancer is critical to understanding underlying pathophysiologic changes in both diseases. Understanding this relationship could allow clinicians to provide proper assessment of cancer risk in patients with PD and might also have implications for the counseling of relatives of patients," the authors note in the study background.

Seth A. Kareus, M.D., and colleagues from the University of Utah, Salt Lake City, estimated relative risks (RRs) for cancer in individuals with PD listed on their death certificate, and in their relatives. The study identified 2,998 patients with PD listed as their cause of death from 1904 to 2008 and also included information from the Utah Cancer Registry on 100,817 patients diagnosed with cancer.

To validate their observed associations, researchers also estimated the reciprocal RR for PD death among patients diagnosed with melanoma and their relatives, and estimated the RRs for death with PD among patients diagnosed with prostate cancer and their relatives.

"A significantly increased risk for prostate cancer was observed in the PD population as well as among their relatives. A reciprocal significantly increased risk for PD was also found in the 22,147 prostate cancer cases and their relatives," according to the study results.

The study also notes that "a significantly elevated risk for melanoma was found in the Utah PD population as well as in their relatives. A reciprocal significantly increased relative risk for PD was found in 7,841Utahmelanoma cases and their relatives," the study results indicate.

Among the individuals with PD who died, the authors observed 48 cases of melanoma. The estimated RR for melanoma in patients with PD who died was 1.95; and an increased risk for death with PD was noted among the patients with melanoma (RR, 1.65). Researchers also found prostate cancer in 212 patients with PD who died (RR, 1.71) and an increased risk for death with PD was found among the prostate cancer patients (RR, 1.39), according to the results.

"Thus, these data argue strongly for a significant shared genetic risk for specific cancers on the one hand and neurodegeneration on the other. ….These studies provide a framework for future definition of the precise nature of shared genetic variation leading to neurodegeneration in some individuals, but skin or prostate cancers in others, and they may influence strategies for skin and prostate cancer screening," the authors conclude.

Editorial: Families with Parkinson Disease, Cancer

In an editorial, Walter A. Rocca, M.D., M.P.H., of the Mayo Clinic, Rochester, Minn., writes: "The findings from Kareus et al, combined with previous findings in the literature, suggest that some families have a genetic predisposition that can manifest as PD, as other types of parkinsonism, as essential tremor, as cognitive impairment or dementia, as amyotrophic lateral sclerosis, as anxiety disorders, as depressive disorders, or as nonneurological conditions such as melanoma and prostate cancer."

"If the mechanisms are primarily genetic, as suggested by Kareus and colleagues, then it may be possible to identify genetic variants that predispose to accelerated neurodegeneration and to increased oncogenesis in the same individual or among members of some particular families," Rocca continues.

"On the other hand, if PD is multifactorial at the individual level, dimorphic in men and women, and heterogeneous at the population level, the search for one or several genetic variants may not be productive," Rocca concludes.

Journal References:

  1. Kareus SA, Figueroa KP, Cannon-Albright LA, Pulst SM. Shared Predispositions of Parkinsonism and Cancer: A Population-Based Pedigree-Linked Study. Archives of Neurology, 2012; DOI: 10.1001/archneurol.2012.2261
  2. Walter A. Rocca. Families With Parkinson Disease and Cancer. Archives of Neurology, 2012; DOI: 10.1001/archneurol.2012.2664

Therapeutic avenues for Parkinson's investigated

Scientists at the University of Houston (UH) have discovered what may possibly be a key ingredient in the fight against Parkinson's disease.

Affecting more than 500,000 people in the U.S., Parkinson's disease is a degenerative disorder of the central nervous system marked by a loss of certain nerve cells in the brain, causing a lack of dopamine. These dopamine-producing neurons are in a section of the midbrain that regulates body control and movement. In a study recently published in the Proceedings of the National Academy of Sciences (PNAS), researchers from the UH Center for Nuclear Receptors and Cell Signaling (CNRCS) demonstrated that the nuclear receptor liver X receptor beta (LXRbeta) may play a role in the prevention and treatment of this progressive neurodegenerative disease.

"LXRbeta performs an important function in the development of the central nervous system, and our work indicates that the presence of LXRbeta promotes the survival of dopaminergic neurons, which are the main source of dopamine in the central nervous system," said CNRCS director and professor Jan-Åke Gustafsson, whose lab discovered LXRbeta in 1995. "The receptor continues to show promise as a potential therapeutic target for this disease, as well as other neurological disorders."

To better understand the relationship between LXRbeta and Parkinson's disease, the team worked with a potent neurotoxin, called MPTP, a contaminant found in street drugs that caused Parkinson's in people who consumed these drugs. In lab settings, MPTP is used in murine models to simulate the disease and to study its pathology and possible treatments.

The researchers found that the absence of LXRbeta increased the harmful effects of MPTP on dopamine-producing neurons. Additionally, they found that using a drug that activates LXRbeta receptors prevented the destructive effects of MPTP and, therefore, may offer protection against the neurodegeneration of the midbrain.

"LXRbeta is not expressed in the dopamine-producing neurons, but instead in the microglia surrounding the neurons," Gustafsson said. "Microglia are the police of the brain, keeping things in order. In Parkinson's disease the microglia are overactive and begin to destroy the healthy neurons in the neighborhood of those neurons damaged by MPTP. LXRbeta calms down the microglia and prevents collateral damage. Thus, we have discovered a novel therapeutic target for treatment of Parkinson's disease."

Journal Reference:

  1. Y.-b. Dai, X.-j. Tan, W.-f. Wu, M. Warner, J.-A. Gustafsson. Liver X receptor   protects dopaminergic neurons in a mouse model of Parkinson disease. Proceedings of the National Academy of Sciences, 2012; 109 (32): 13112 DOI: 10.1073/pnas.1210833109