Featured Research

from universities, journals, and other organizations

Excess protein linked to development of Parkinson's disease

Date:
February 7, 2013
Source:
University of California, San Diego Health Sciences
Summary:
Researchers 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.

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: Image courtesy of the 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.

Co-authors are Monica L. Berlanga, Masako Terada, Junru Hu, Eric A. Bushong and Minju Hwang, National Center for Microscopy and Imaging Research and Center for Research on Biological Systems; Mary Ann Yang and Julia M. George, Department of Cell and Developmental Biology, University of Illinois, Urbana; and Eliezer Masliah, Department of Neurosciences, UCSD.

Funding for this research came, in part, from the NIH National Center for Research Resources (5P41RR004050-24), the National Institute of General Medical Sciences (8 P41 GM103412-24), National Institutes of Health grants R01 GM086197-05, AG184440 and AG022074, as well as support from the Branfman Family Foundation and the Institute for Systems Biology, as part of the activities of a consortium of researchers linked to the Luxembourg Center for Systems Biomedicine's research program on neurodegenerative disease.


Story Source:

The above story is based on materials provided by University of California, San Diego Health Sciences. Note: Materials may be edited for content and length.


Journal Reference:

  1. D. Boassa, M. L. Berlanga, M. A. Yang, M. Terada, J. Hu, E. A. Bushong, M. Hwang, E. Masliah, J. M. George, M. H. Ellisman. Mapping the Subcellular Distribution of -Synuclein in Neurons using Genetically Encoded Probes for Correlated Light and Electron Microscopy: Implications for Parkinson's Disease Pathogenesis. Journal of Neuroscience, 2013; 33 (6): 2605 DOI: 10.1523/JNEUROSCI.2898-12.2013

Cite This Page:

University of California, San Diego Health Sciences. "Excess protein linked to development of Parkinson's disease." ScienceDaily. ScienceDaily, 7 February 2013. <www.sciencedaily.com/releases/2013/02/130207141402.htm>.
University of California, San Diego Health Sciences. (2013, February 7). Excess protein linked to development of Parkinson's disease. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2013/02/130207141402.htm
University of California, San Diego Health Sciences. "Excess protein linked to development of Parkinson's disease." ScienceDaily. www.sciencedaily.com/releases/2013/02/130207141402.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Microneedle Patch Promises Painless Pricks

Microneedle Patch Promises Painless Pricks

Reuters - Innovations Video Online (Oct. 18, 2014) Researchers at The National University of Singapore have invented a new microneedle patch that could offer a faster and less painful delivery of drugs such as insulin and painkillers. Video provided by Reuters
Powered by NewsLook.com
Raw: Nurse Nina Pham Arrives in Maryland

Raw: Nurse Nina Pham Arrives in Maryland

AP (Oct. 17, 2014) The first nurse to be diagnosed with Ebola at a Dallas hospital walked down the stairs of an executive jet into an ambulance at an airport in Frederick, Maryland, on Thursday. Pham will be treated at the National Institutes of Health. (Oct. 16) Video provided by AP
Powered by NewsLook.com
Raw: Cruise Ship Returns to US Over Ebola Fears

Raw: Cruise Ship Returns to US Over Ebola Fears

AP (Oct. 17, 2014) A Caribbean cruise ship carrying a Dallas health care worker who is being monitored for signs of the Ebola virus is heading back to Texas, US, after being refused permission to dock in Cozumel, Mexico. (Oct. 17) Video provided by AP
Powered by NewsLook.com
Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

AFP (Oct. 17, 2014) All four suspected Ebola cases admitted to hospitals in Spain on Thursday have tested negative for the deadly virus in a first round of tests, the government said Friday. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins