Protein regulates neuronal communication by self-association
The protein alpha-synuclein is a well-known player in Parkinson's disease and other related neurological conditions, such as dementia with Lewy bodies. Its normal functions, however, have long remained unknown. An enticing mystery, say researchers, who contend that understanding the normal is critical in resolving the abnormal.
Alpha-synuclein typically resides at presynaptic terminals – the communication hubs of neurons where neurotransmitters are released to other neurons. In previous studies, Subhojit Roy, MD, PhD, and colleagues at the University of California, San Diego School of Medicine had reported that alpha-synuclein diminishes neurotransmitter release, suppressing communication among neurons. The findings suggested that alpha-synuclein might be a kind of singular brake, helping to prevent unrestricted firing by neurons. Precisely how, though, was a mystery.
Then Harvard University researchers reported in a recent study that alpha-synuclein self-assembles multiple copies of itself inside neurons, upending an earlier notion that the protein worked alone. And in a new paper, published this month in Current Biology, Roy, a cell biologist and neuropathologist in the departments of Pathology and Neurosciences, and co-authors put two and two together, explaining how these aggregates of alpha-synuclein, known as multimers, might actually function normally inside neurons.
First, they confirmed that alpha-synuclein multimers do in fact congregate at synapses, where they help cluster synaptic vesicles and restrict their mobility. Synaptic vesicles are essentially tiny packages created by neurons and filled with neurotransmitters to be released. By clustering these vesicles at the synapse, alpha-synuclein fundamentally restricts neurotransmission. The effect is not unlike a traffic light – slowing traffic down by bunching cars at street corners to regulate the overall flow.
"In normal doses, alpha-synuclein is not a mechanism to impair communication, but rather to manage it. However it's quite possible that in disease, abnormal elevations of alpha-synuclein levels lead to a heightened suppression of neurotransmission and synaptic toxicity," said Roy.
"Though this is obviously not the only event contributing to overall disease neuropathology, it might be one of the very first triggers, nudging the synapse to a point of no return. As such, it may be a neuronal event of critical therapeutic relevance."
Indeed, Roy noted that alpha-synuclein has become a major target for potential drug therapies attempting to reduce or modify its levels and activity.
Co-authors include Lina Wang, Utpal Das and Yong Tang, UCSD; David Scott, Massachusetts Institute of Technology; and Pamela J. McLean, Mayo Clinic-Jacksonville.
Funding support for this research came from National Institutes of Health (grant P50AG005131-project 2) and the UC San Diego Alzheimer's Disease Research Center.
Scott LaFee | Eurek Alert!
How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH
A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
23.06.2017 | Physics and Astronomy
23.06.2017 | Physics and Astronomy
23.06.2017 | Information Technology