Finding that may result in new treatments for the debilitating disorder
A team of UCLA researchers has identified a new gene involved in Parkinson's disease, a finding that may one day provide a target for a new drug to prevent and potentially even cure the debilitating neurological disorder.
This is Dr. Ming Guo.
Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease, and there is no cure for the progressive and devastating illness. About 60,000 Americans are diagnosed with Parkinson's disease each year. It is estimated that as many as 1 million Americans live with Parkinson's disease, which is more than the number of people diagnosed with multiple sclerosis, muscular dystrophy and Lou Gehrig's disease combined.
In Parkinson's disease, multiple neurons in the brain gradually break down or die. This leads to the movement impairments, such as tremor, rigidity, slowness in movement and difficulty walking, as well as depression, anxiety, sleeping difficulties and dementia, said Dr. Ming Guo, the study team leader, associate professor of neurology and pharmacology and a practicing neurologist at UCLA.
A handful of genes have been identified in inherited cases of Parkinson's disease. Guo's team was one of two groups worldwide that first reported in 2006 in the journal Nature that two of these genes, PTEN-induced putative kinase 1 (PINK1) and PARKIN, act together to maintain the health of mitochondria – the power house of the cell that is important in maintaining brain health. Mutations in these genes lead to early-onset Parkinson's disease.
Guo's team has further shown that when PINK1 and PARKIN are operating correctly, they help maintain the regular shape of healthy mitochondria and promote elimination of damaged mitochondria. Accumulation of unhealthy or damaged mitochondria in neurons and muscles ultimately results in Parkinson's disease.
In this study, the team found that the new gene, called MUL1 (also known as MULAN and MAPL), plays an important role in mediating the pathology of the PINK1 and PARKIN. The study, performed in fruit flies and mice, showed that providing an extra amount of MUL1 ameliorates the mitochondrial damage due to mutated PINK/PARKIN, while inhibiting MUL1 in mutant PINK1/PARKIN exacerbates the damage to the mitochondria. In addition, Guo and her collaborators found that removing MUL1 from mouse neurons of the PARKIN disease model results in unhealthy mitochondria and degeneration of the neurons.
The five-year study appears June 4, 2014, in eLife, a new, open access scientific journal for groundbreaking biomedical and life research sponsored by the Howard Hughes Medical Institute (United States), the Wellcome Trust (United Kingdom) and Max Plank Institutes (Germany).
"We are very excited about this finding," Guo said. "There are several implications to this work, including that MUL1 appears to be a very promising drug target and that it may constitute a new pathway regulating the quality of mitochondria."
Guo characterized the work as "a major advancement in Parkinson's disease research."
"We show that MUL1 dosage is key and optimizing its function is crucial for brain health and to ward off Parkinson's disease," she said. "Our work proves that mitochondrial health is of central importance to keep us from suffering from neurodegeneration. Further, finding a drug that can enhance MUL1 function would be of great benefit to patients with Parkinson's disease."
Going forward, Guo and her team will test these results in more complex organisms, hoping to uncover additional functions and mechanisms of MUL1. Additionally, the team will perform small molecule screens to help identify potential compounds that specifically target MUL1. Further, they will examine if mutations in MUL1 exist in some patients with inherited forms of Parkinson's.
The study, collaboration between the Guo lab and Dr. Zuhang Sheng from the National Institute of Health, was supported by the National Institute of Aging (R01, K02), National Institute of Neurological Disorders and Stroke (EUREKA award), Ellison Medical Foundation Senior Scholar Award, McKnight Neuroscience Foundation, the Klingenstein Foundation, the American Parkinson's Disease Association and the Glenn Family Foundation.
The UCLA Department of Neurology encompasses more than 26 disease-related research programs. This includes all of the major categories of neurological diseases and methods, encompassing neurogenetics and neuroimaging, as well as health services research. The 140 faculty members of the department are distinguished scientists and clinicians who have been ranked No. 1 in National Institutes of Health funding since 2002. The department is dedicated to understanding the human nervous system and improving the lives of people with neurological diseases, focusing on three key areas: patient/clinical care, research and education.
Kim Irwin | Eurek Alert!
What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society
Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
23.08.2017 | Life Sciences
23.08.2017 | Life Sciences
23.08.2017 | Physics and Astronomy