The work is published in today's issue of Nature Communications. Lead author is Makoto Hashimoto of the Division of Chemistry and Metabolism, Tokyo Metropolitan Institute for Neuroscience, with colleagues including Eliezer Masliah, MD, professor of neurosciences and pathology in the UC San Diego School of Medicine, Edward Rockenstein, a research associate in UCSD's Experimental Neuropath Laboratory and Albert R. La Spada, MD, PhD, professor of cellular and molecular medicine, chief of the Division of Genetics in the Department of Pediatrics and associate director of the Institute for Genomic Medicine at UC San Diego.
In 2004, La Spada discovered mutations in a family afflicted with a neurological disorder known as Dementia with Lewy Bodies. DLB is one of the most common types of progressive dementia, combining features of both Alzheimer's and Parkinson's diseases. Lewy bodies are abnormal aggregates of proteins. There are no known therapies to stop or slow the DLB's progression. There is no cure.
In the 2004 study, La Spada and colleagues found that mutations of the naturally occurring B-synuclein protein in DLB patients "were strong strongly suggestive of being pathogenic." That is, the mutated protein caused or was a cause of the disease. But the findings were not definitive.
The newly published research describes the creation of a transgenic mouse model that expresses the B-synuclein mutation. The mice suffer from neurodegenerative disease, validating La Spada's earlier work.
"Beta-synuclein is interesting because it is closely related to alpha-synuclein, a protein that can cause Parkinson's disease by being mutated or over-expressed," said La Spada. "A-synuclein is viewed as central to Parkinson's disease pathogenesis. The question has been: could B-synuclein also promote neurodegeneration because it's similar in its sequence and expression pattern to A-synuclein? This study shows that the answer is yes."
These findings, said La Spada, establish B-synuclein's links to Parkinson's disease and related disorders, making it a new and, now, proven target for potential therapies.
Co-authors of the study are Masaya Fujita, Shuei Sugama, Kazunari Sekiyama, Akio Sekigawa, Masaaki Nakai, Masaaki Waragai, Yoshiki Takamatsu and Jianshe Wei of the Division of Chemistry and Metabolism, Tokyo Metropolitan Institute for Neuroscience; Tohru Tsukui of the Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University; Takato Takenouchi of the Division of Chemistry and Metabolism, Tokyo Metropolitan Institute for Neuroscience and the Transgenic Animal Research Center, National Institute of Agrobiological Sciences in Japan; and Satoshi Inoue of Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University and Department of Anti-Aging, Graduate School of Medicine, University of Tokyo.
Funding for this study came in part from grants by Science Research, the Cell Innovation Project; Challenging Exploratory Research, the National Institute of Biomedical Innovation, the Takeda Foundation, the Novartis Foundation for Gerontological Research and the National Institutes of Health.
Scott LaFee | EurekAlert!
Fine organic particles in the atmosphere are more often solid glass beads than liquid oil droplets
21.04.2017 | Max-Planck-Institut für Chemie
Study overturns seminal research about the developing nervous system
21.04.2017 | University of California - Los Angeles Health Sciences
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...
Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.
A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
21.04.2017 | Physics and Astronomy
21.04.2017 | Health and Medicine
21.04.2017 | Physics and Astronomy