Featured Research

from universities, journals, and other organizations

Parkinson's disease protein gums up garbage disposal system in cells

Date:
March 28, 2013
Source:
University of Pennsylvania School of Medicine
Summary:
With a new neuron model system of Parkinson's disease pathologies, researchers have demonstrated that these aberrant clumps in cells resist degradation as well as impair the function of the macroautophagy system, one of the major garbage disposal systems within the cell.

This shows lewy bodies. Brown spots are immunostaining using an antibody specifically recognizing an abnormal form of alpha-synuclein.
Credit: Kelvin C. Luk, Ph.D., Perelman School of Medicine, University of Pennsylvania

Clumps of α-synuclein protein in nerve cells are hallmarks of many degenerative brain diseases, most notably Parkinson's disease.

"No one has been able to determine if Lewy bodies and Lewy neurites, hallmark pathologies in Parkinson's disease can be degraded," says Virginia Lee, PhD, director of the Center for Neurodegenerative Disease Research, at the Perelman School of Medicine, University of Pennsylvania.

"With the new neuron model system of Parkinson's disease pathologies our lab has developed recently, we demonstrated that these aberrant clumps in cells resist degradation as well as impair the function of the macroautophagy system, one of the major garbage disposal systems within the cell."

Macroautophagy, literally self eating, is the degradation of unnecessary or dysfunctional cellular bits and pieces by a compartment in the cell called the lysosome.

Lee, also a professor of Pathology and Laboratory Medicine, and colleagues published their results in the early online edition of the Journal of Biological Chemistry this week.

Alpha-synuclein (α-syn ) diseases all have clumps of the protein and include Parkinson's disease (PD), and array of related disorders: PD with dementia , dementia with Lewy bodies, and multiple system atrophy. In most of these, α-syn forms insoluble aggregates of stringy fibrils that accumulate in the cell body and extensions of neurons.

These unwanted α-syn clumps are modified by abnormal attachments of many phosphate chemical groups as well as by the protein ubiquitin, a molecular tag for degradation. They are widely distributed in the central nervous system, where they are associated with neuron loss.

Using cell models in which intracellular α-syn clumps accumulate after taking up synthetic α-syn fibrils, the team showed that α-syn inclusions cannot be degraded, even though they are located near the lysosome and the proteasome, another type of garbage disposal in the cell.

The α-syn aggregates persist even after soluble α-syn levels within the cell are substantially reduced, suggesting that once formed, the α-syn inclusions are resistant to being cleared. What's more, they found that α-syn aggregates impair the overall autophagy degradative process by delaying the maturation of autophagy machines known as autophagosomes, which may contribute to the increased cell death seen in clump-filled nerve cells. Understanding the impact of α-syn aggregates on autophagy may help elucidate therapies for α-syn-related neurodegeneration.

Co-authors are Selcuk A. Tanik, Christine E. Schultheiss, Laura A. Volpicelli-Daley, and Kurt R. Brunden, all from Penn.

This research was funded by the National Institutes of Neurological Diseases (NS053488), the JPB Foundation, and the Jeff and Anne Keefer Fund.


Story Source:

The above story is based on materials provided by University of Pennsylvania School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. S. A. Tanik, C. E. Schultheiss, L. A. Volpicelli-Daley, K. R. Brunden, V. M. Y. Lee. Lewy body-like -synuclein aggregates resist degradation and impair macroautophagy. Journal of Biological Chemistry, 2013; DOI: 10.1074/jbc.M113.457408

Cite This Page:

University of Pennsylvania School of Medicine. "Parkinson's disease protein gums up garbage disposal system in cells." ScienceDaily. ScienceDaily, 28 March 2013. <www.sciencedaily.com/releases/2013/03/130328125232.htm>.
University of Pennsylvania School of Medicine. (2013, March 28). Parkinson's disease protein gums up garbage disposal system in cells. ScienceDaily. Retrieved April 19, 2014 from www.sciencedaily.com/releases/2013/03/130328125232.htm
University of Pennsylvania School of Medicine. "Parkinson's disease protein gums up garbage disposal system in cells." ScienceDaily. www.sciencedaily.com/releases/2013/03/130328125232.htm (accessed April 19, 2014).

Share This



More Mind & Brain News

Saturday, April 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Study On Artists' Brain Shows They're 'Structurally Unique'

Study On Artists' Brain Shows They're 'Structurally Unique'

Newsy (Apr. 17, 2014) The brains of artists aren't really left-brain or right-brain, but rather have extra neural matter in visual and motor control areas. Video provided by Newsy
Powered by NewsLook.com
Is Apathy A Sign Of A Shrinking Brain?

Is Apathy A Sign Of A Shrinking Brain?

Newsy (Apr. 17, 2014) A recent study links apathetic feelings to a smaller brain. Researchers say the results indicate a need for apathy screening for at-risk seniors. Video provided by Newsy
Powered by NewsLook.com
Are School Dress Codes Too Strict?

Are School Dress Codes Too Strict?

AP (Apr. 16, 2014) Pushing the limits on style and self-expression is a rite of passage for teens and even younger kids. How far should schools go with their dress codes? The courts have sided with schools in an era when school safety is paramount. (April 16) Video provided by AP
Powered by NewsLook.com
Could Even Casual Marijuana Use Alter Your Brain?

Could Even Casual Marijuana Use Alter Your Brain?

Newsy (Apr. 16, 2014) A new study conducted by researchers at Northwestern and Harvard suggests even casual marijuana use can alter your brain. Video provided by Newsy
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:
from the past week

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