Excess protein linked to development of Parkinson's disease
Using serial block face scanning electron microscopy and other technologies, researchers created three-dimensional images of the neocortex of transgenic mice engineered to over-express the human protein, alpha-synuclein, and noted massively enlarged nerve terminals. In this image, an over-sized terminal (green) forms a synapse (red) with a dendritic spine (golden). A normal and smaller terminal (blue) forms a synapse with an adjacent spine on the same dendrite. Credit: National Center for Microscopy and Imaging Research, UC San Diego
Researchers at the University of California, San Diego School of Medicine say overexpression of a protein called alpha-synuclein appears to disrupt vital recycling processes in neurons, starting with the terminal extensions of neurons and working its way back to the cells' center, with the potential consequence of progressive degeneration and eventual cell death.
The findings, published in the February 6, 2013 issue of the Journal of Neuroscience, have major implications for more fully understanding the causes and mechanisms of Parkinson's disease (PD), a neurodegenerative movement disorder that affects an estimated one million Americans.
"This is an important new insight. I don't think anybody realized just how big a role alpha-synuclein played in managing the retrieval of worn-out proteins from synapses and the role of alterations in this process in development of PD," said principal investigator Mark H. Ellisman, PhD, professor of neurosciences and bioengineering and director of the National Center for Microscopy and Imaging Research (NCMIR), based at UC San Diego.
Parkinson's disease is characterized by the gradual destruction of select brain cells that produce dopamine, a neurotransmitter involved in regulating movement and emotion. Symptoms include increasing loss of muscle and movement control. While most cases are sporadic – that is, their causes are unknown – there are also inherited forms of PD linked to specific gene mutations and modifications.
The UC San Diego researchers, with colleagues at the University of Illinois, Urbana, focused upon one of those gene products: alpha-synuclein. Using a variety of leading-edge imaging technologies, including a new fluorescent tagging technique developed for electron microscopy by UC San Diego Nobel laureate Roger Tsien's lab and colleagues at NCMIR, the scientists created three-dimensional maps of alpha-synuclein distribution both in cultured neurons and in the neurons of mice engineered to over-express the human protein.
They found that excess levels of alpha-synuclein accumulated in the presynaptic terminal – part of the junction where axons and dendrites of brain cells meet to exchange chemical signals.
"The over-expression of alpha-synuclein caused hypertrophy in these terminals," said Daniela Boassa, PhD, a research scientist at NCMIR and the study's first author. "The terminals were enlarged, filled with structures we normally don't see."
Boassa said that as alpha-synuclein accumulates in the terminals, it appears to hinder normal degradation and recycling processes in neurons. This would progressively impair the release of neurotransmitters. In time, the neurons might simply stop functioning and die.
"Other studies have noted that PD is characterized by progressive loss of vesicle traffic, and neurotransmitter release," Boassa said. "Our study provides a structural and mechanistic explanation for why that happens."
Boassa said the findings shed greater light upon how PD is caused, at least in some heritable forms. Researchers plan to now probe more deeply into how the disease is propagated and how dysfunctional alpha-synuclein proteins spread from one neuron to another, hastening the advance of the disorder.
"The better we understand the mechanisms of PD, the easier it will be to develop clinical interventions," she said.
Journal reference: Journal of Neuroscience
Provided by University of California - San Diego
- SUMO defeats protein aggregates that typify Parkinson's disease Jul 11, 2011 | not rated yet | 0
- Lessons from yeast: A possible cure for Parkinson's disease? Aug 14, 2008 | not rated yet | 0
- Mechanism that leads to sporadic Parkinson's disease identified Sep 25, 2012 | not rated yet | 0
- Protein build-up leads to neurons misfiring Jul 18, 2012 | not rated yet | 0
- Supercomputer simulations may pinpoint causes of Parkinson's, Alzheimer's diseases Mar 22, 2007 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Image of a Convex Lens Cut in Half Horizontally
2 hours ago Hello everyone, A friend of mine came up with this question in class and I really do not have a good answer. Suppose you have a convex lens...
Ray tracing throught optical system of thick lenses
2 hours ago Can you advise me a free software that allow to draw rays passed throught system of thick lenses (preferable in 3D)?
Faraday's law on circular wire
3 hours ago In my examples on Faraday's law in my book, they use a drawing of a magnet approaching a circular wire. The changing magnetic flux then induces an...
Specific Exergy vs Specific Flow Exergy
5 hours ago I'm having some difficulty understanding exactly what the difference between the definitions of these values are. As I understand it, in terms of...
The Durability of Bone: Long Falls
13 hours ago I am doing a paper on the physics in Valve's Portal and got interested in the "Long Fall Boots" that prevent any damage no matter how far you fall. I...
Is energy convertible to matter?
15 hours ago Can we convert energy to matter?
- More from Physics Forums - Classical Physics
More news stories
Parkinson's disease (PD) is a degenerative neurological disorder marked by a progressive loss of motor control. Despite intensive research, there are currently no approved therapies that have been demonstrated to alter the ...
Parkinson's & Movement disorders May 20, 2013 | not rated yet | 0
Faulty energy production in brain cells leads to disorders ranging from Parkinson's to intellectual disability
Neuroscientist Patrik Verstreken of VIB (Flanders Institute for Biotechnology) and KU Leuven has shown for the first time that dysfunctional mitochondria in brain cells can lead to learning disabilities. The link between ...
Parkinson's & Movement disorders May 17, 2013 | 4 / 5 (2) | 0
McGill University researchers have unlocked a new door to developing drugs to slow the progression of Parkinson's disease. Collaborating teams led by Dr. Edward A. Fon at the Montreal Neurological Institute and Hospital -The ...
Parkinson's & Movement disorders May 09, 2013 | 5 / 5 (1) | 0 |
New research reveals that Solanaceae—a flowering plant family with some species producing foods that are edible sources of nicotine—may provide a protective effect against Parkinson's disease. The study appearing today ...
Parkinson's & Movement disorders May 09, 2013 | not rated yet | 0
(Medical Xpress)—Researchers at the Stanford University School of Medicine have exposed the possible function, in the healthy brain, of a mysterious molecule that has been strongly implicated in Parkinson's ...
Parkinson's & Movement disorders May 01, 2013 | 5 / 5 (3) | 0 |
The new 13-valent pneumococcal conjugate vaccine (PCV13) appears to be as safe as the previous version used prior to 2010, the 7-valent pneumococcal conjugate vaccine (PCV7), according to a Kaiser Permanente study published ...
30 minutes ago | not rated yet | 0
Research presented today shows that high-fructose corn syrup can cause behavioural reactions in rats similar to those produced by drugs of abuse such as cocaine. These results, presented by addiction expert Francesco Leri, ...
1 hour ago | 4 / 5 (1) | 0
Is it permissible to harm one to save many? Those who tend to say "yes" when faced with this classic dilemma are likely to be deficient in a specific kind of empathy, according to a report published in the scientific journal ...
6 hours ago | not rated yet | 0 |
(Medical Xpress)—Scientists supported by the National Institutes of Health have a new theory as to why a woman's fertility declines after her mid-30s. They also suggest an approach that might help slow ...
3 hours ago | not rated yet | 0 |
Phthalates: Study links chemicals widely found in plastics, processed food to elevated blood pressure in children, teens
Plastic additives known as phthalates (pronounced THAL-ates) are odorless, colorless and just about everywhere: They turn up in flooring, plastic cups, beach balls, plastic wrap, intravenous tubing and—according to the ...
7 hours ago | not rated yet | 1 |
Medical researchers discover new ways to target, develop and design drugs to prevent and treat viral infection
Researchers at the University of Alberta have discovered a new drug target, developed a new drug and identified a new way to design drugs—all of which could be a winning combination in the battle against viruses.
3 hours ago | 4 / 5 (1) | 0 |