Scientists studying rats induced to display a form of Parkinson’s disease discovered that a protein commonly found in brain cells can be toxic if — at one pinpoint location in its amino acid structure — it lacks a chemical compound called a phosphate.
When scientists used gene therapy to simulate a phosphate at this critical position, the rats’ brain cells didn’t develop the Parkinson-like pathology that would normally occur.
The finding provides new insight into the fundamentals of Parkinson’s disease and the role of an abundant yet mysterious brain protein known as alpha-synuclein, which is believed to help brain cells communicate but may have a more sinister role in the development of neurological diseases.
“We have another potential target for therapy, but there is a great deal left to discover,” said Nicholas Muzyczka, Ph.D., a professor of molecular genetics and microbiology in the College of Medicine and an eminent scholar with the UF Genetics Institute. “This is one more piece of information about what might be causing the toxicity in Parkinson’s disease, and it gives us a little more to go on about what alpha-synuclein does in the brain.”
Generally located at the synapses of nerve cells, alpha-synuclein is believed to aid in brain function, possibly by helping cells communicate with one another by controlling the release of neurotransmitters such as dopamine.
Mutations of alpha-synuclein may cause a rare, inherited form of Parkinson’s, and the protein has been found to be the major component of Lewy bodies, which are abnormal clusters of protein in the brain cells of patients with Parkinson’s disease.
The National Parkinson Foundation estimates 1.5 million Americans currently have Parkinson’s disease and about 60,000 new cases are diagnosed each year. It is caused by the death or impairment of certain nerve cells in a part of the brain called the substantia nigra. When these cells die, the body is deprived of dopamine, a neurotransmitter vital for movement.
“We know of several enzymes that can cause phosphorylation in the proper position of the alpha-synuclein protein,” said Oleg Gorbatyuk, Ph.D., an assistant professor of molecular genetics and microbiology. “Increasing their expression in brains afflicted with Parkinson’s disease could possibly provide a gene therapy approach to the disease.”
In experiments described in the Jan. 15 issue of PNAS, UF researchers used gene transfer to enhance the production of three versions of alpha-synuclein in the substantia nigra region on one side of the rats’ brains. The other side was not treated, for comparison purposes.
Of the types of alpha-synuclein, the one that simulated phosphorylation at position 129 of the protein was nontoxic. But the other versions of the protein all caused significant loss of dopamine neurons in the substantia nigra.
“Adding a phosphate group is about the smallest thing that can possibly happen in biology,” said Mark R. Cookson, an investigator in the Cell Biology and Gene Expression Unit of the National Institute on Aging who was not involved in the research. “But this relatively minor, innocuous change can switch everything around from being a big problem to being no problem. This research really gives us an idea of some things going on in inherited cases of Parkinson’s disease, and if we use that genetic information as a handle to get into the common disease, it is possible to take this from genetics to a drug discovery program.”
John D. Pastor | EurekAlert!
Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo
Research reveals how order first appears in liquid crystals
23.05.2018 | Brown University
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...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
23.05.2018 | Life Sciences
23.05.2018 | Life Sciences
23.05.2018 | Physics and Astronomy