A new study demonstrates that high levels of MAO-B, an enzyme that regulates nerve activity in the brain, cause Parkinson’s-like symptoms in mice genetically engineered to overexpress the protein. Furthermore, drugs currently used as an adjunct therapy for Parkinson’s in humans prevented the development of Parkinson’s symptoms in these same animals.
The findings, by scientists at the Buck Institute for Age Research, raise the possibility that humans could be tested to see if they have a risk factor for the progressive, incurable neurodegenerative disorder that affects 1.5 million Americans and receive preventive treatment. The study appears in the February 20 issue of the open-access, online journal, PLoS ONE.
Levels of measurable MAO-B vary 50-fold in humans and tend to increase with age. Several studies have suggested that increases in MAO-B contribute to the neurodegeneration associated with PD, but direct proof of a causative role for the enzyme has been lacking. The drug deprenyl, which inhibits MAO-B, is a longstanding therapy for Parkinson’s used together with drugs that boost the level of dopamine, an important neurotransmitter that is preferentially depleted in the disease. Clinical studies that suggest that deprenyl treatment alone does not impact mortality associated with Parkinson’s have cast doubt on the role of MAO-B in the disease itself. Buck faculty member Julie Andersen, PhD, who led the study says that may not be the case. “Those studies were targeted to patients who already had symptoms of Parkinson’s -- by the time Parkinson’s is symptomatically detectable, dopamine loss is usually at least 60%,” said Andersen. “Therefore the lack of effectiveness of MAO-B inhibition in these patients does not negate a role for MAO-B increase in disease development.” Andersen added, “We have demonstrated that elevations in MAO-B result in selective loss of neurons associated with Parkinson’s in a mouse model and that the severity of this loss is age-dependent.”
Tests to measure levels of MAO-B are not currently available to the general public, although enzyme levels are tracked in clinical trials. Andersen says MAO-B testing could be akin to current practices involving cholesterol, which is measured and monitored as a risk factor for cardiovascular disease. “However, it is important to note that Parkinson’s is a multi-factor disease,” said Andersen. “The fact that someone has high levels of MAO-B does not necessarily mean they are fated to develop Parkinson’s.”
Andersen said results of the study point to the need for an early diagnostic test for Parkinson’s. "Currently, by the time people are diagnosed with the disease they have already lost 60% of the neurotransmitter levels implicated in Parkinson’s; treatment with a drug like deprenyl would likely be most effective if taken before symptoms appear in order to halt disease progression."
The novel transgenic mouse line created for this study provides a new model for exploring molecular pathways involved in the initiation or early progression of several key features associated with Parkinson’s pathology including dopaminergic midbrain cell loss. The mouse line also allows for additional therapeutic drug testing.
Joining Andersen in the study were Jyothi K. Mallajosyula, Deepinder Kaur, Shankar J. Chinta, Subramanian Rajagopalan, Anand Rane, and David G. Nicholls of the Buck Institute, along with Dino DiMonte of the Parkinson’s Institute and Heather Macarthur of the Saint Louis University School of Medicine. The work was funded by the National Institutes of Health (R01 NS40057-04) and the National Parkinson’s Foundation.
The Buck Institute is an independent non-profit organization dedicated to extending the healthspan, the healthy years of each individual’s life. The National Institute of Aging designated the Buck a Nathan Shock Center of Excellence in the Biology of Aging, one of just five centers in the country. Buck Institute scientists work in an innovative, interdisciplinary setting to understand the mechanisms of aging and to discover new ways of detecting, preventing and treating age-related diseases such as Alzheimer’s and Parkinson’s disease, cancer, stroke, and arthritis. Collaborative research at the Institute is supported by genomics, proteomics and bioinformatics technology.
WAKE-UP provides new treatment option for stroke patients | International study led by UKE
17.05.2018 | Universitätsklinikum Hamburg-Eppendorf
First form of therapy for childhood dementia CLN2 developed
25.04.2018 | Universitätsklinikum Hamburg-Eppendorf
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
25.05.2018 | Event News
02.05.2018 | Event News
13.04.2018 | Event News
25.05.2018 | Event News
25.05.2018 | Machine Engineering
25.05.2018 | Life Sciences