Featured Research

from universities, journals, and other organizations

Scientists identify 'clean-up' snafu that kills brain cells in Parkinson's disease

Date:
March 3, 2013
Source:
Albert Einstein College of Medicine of Yeshiva University
Summary:
Researchers have discovered how the most common genetic mutations in familial Parkinson’s disease damage brain cells.

Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered how the most common genetic mutations in familial Parkinson's disease damage brain cells. The study, which published online today in the journal Nature Neuroscience, could also open up treatment possibilities for both familial Parkinson's and the more common form of Parkinson's that is not inherited.

Parkinson's disease is a gradually progressing disorder of the nervous system that causes stiffness or slowing of movement. According to the Parkinson's Disease Foundation, as many as one million Americans are living with the disease.

The most common mutations responsible for the familial form of Parkinson's disease affect a gene called leucine-rich repeat kinase-2 (LRRK2). The mutations cause the LRRK2 gene to code for abnormal versions of the LRRK2 protein. But it hasn't been clear how LRRK2 mutations lead to the defining microscopic sign of Parkinson's: the formation of abnormal protein aggregates inside dopamine-producing nerve cells of the brain.

"Our study found that abnormal forms of LRRK2 protein disrupt an important garbage-disposal process in cells that normally digests and recycles unwanted proteins including one called alpha-synuclein -- the main component of those protein aggregates that gunk up nerve cells in Parkinson's patients," said study leader Ana Maria Cuervo, M.D., Ph.D., professor of developmental and molecular biology, of anatomy and structural biology, and of medicine and the Robert and Renee Belfer Chair for the Study of Neurodegenerative Diseases at Einstein.

The name for the disrupted disposal process is chaperone-mediated autophagy (the word "autophagy" literally means "self-eating"). It involves specialized molecules that "guide" old and damaged proteins to enzyme-filled structures called lysosomes; there the proteins are digested into amino acids, which are then recycled within the cell.

"We showed that when LRRK2 inhibits chaperone-mediated autophagy, alpha-synuclein doesn't get broken down and instead accumulates to toxic levels in nerve cells," said Dr. Cuervo.

The study involved mouse neurons in tissue culture from four different animal models, neurons from the brains of patients with Parkinson's with LRRK2 mutations, and neurons derived from the skin cells of Parkinson's patients via induced pluripotent stem (iPS) cell technology. All the lines of research confirmed the researchers' discovery.

"We're now looking at ways to enhance the activity of this recycling system to see if we can prevent or delay neuronal death and disease," said Dr. Cuervo. "We've started to analyze some chemical compounds that look very promising."

Dr. Cuervo hopes that such treatments could help patients with familial as well as nonfamilial Parkinson's -- the predominant form of the disease that also involves the buildup of alpha-synuclein.

Dr. Cuervo is credited with discovering chaperone-mediated autophagy. She has published extensively on autophagy and its role in numerous diseases, such as Huntington's disease, and its role in age-related conditions, including organ decline and weakened immunity. Dr. Cuervo is co-director of Einstein's Institute of Aging Research.

The paper is titled "Interplay of LRRK2 with chaperone-mediated autophagy." In addition to Dr. Cuervo, other Einstein contributors include Samantha J. Orenstein, a graduate student who performed most of this study as part of her Ph.D. thesis; Inmaculada Tasset, Ph.D.; Esperanza Arias, Ph.D.; and Hiroshi Koga, Ph.D., all members of Dr. Cuervo's group. Additional co-authors are: Sheng-Hang Kuo Ph.D., David Sulzer Ph.D., Etty Cortes, M.D., and Lawrence S. Honig, M.D. (Columbia University, NY); William Dauer, M.D., (University of Michigan, Ann Arbor, MI); Irene Fernandez-Carasa and Antonella Consiglio, Ph.D., (University of Barcelona, Barcelona Spain); and Angel Raya, M.D., Ph.D., (Institucio Catalana de Recerca I Estudies Avancas, Barcelona, Spain).

This work was supported by grants from the National Institute on Aging (AG031782 and AG08702), the National Institute of Neurological Disorders and Stroke Udall Center of Excellence both part of the National Institutes of Health; The Rainwaters Foundation, The Beatrice and Roy Backus Foundation, JPB Foundation; Parkinson's Disease Foundation; Fondazione Guido Berlucchi; Centers for Networked Biomedical Research; Ministry of Economy and Competitiveness; a Hirschl/Weill-Caulier Career Scientist Award; and a gift from Robert and Renee Belfer.


Story Source:

The above story is based on materials provided by Albert Einstein College of Medicine of Yeshiva University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Samantha J Orenstein, Sheng-Hang Kuo, Inmaculada Tasset, Esperanza Arias, Hiroshi Koga, Irene Fernandez-Carasa, Etty Cortes, Lawrence S Honig, William Dauer, Antonella Consiglio, Angel Raya, David Sulzer and Ana Maria Cuervo. Interplay of LRRK2 with chaperone-mediated autophagy. Nature Neuroscience, 03 March 2013 DOI: 10.1038/nn.3350

Cite This Page:

Albert Einstein College of Medicine of Yeshiva University. "Scientists identify 'clean-up' snafu that kills brain cells in Parkinson's disease." ScienceDaily. ScienceDaily, 3 March 2013. <www.sciencedaily.com/releases/2013/03/130303154850.htm>.
Albert Einstein College of Medicine of Yeshiva University. (2013, March 3). Scientists identify 'clean-up' snafu that kills brain cells in Parkinson's disease. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2013/03/130303154850.htm
Albert Einstein College of Medicine of Yeshiva University. "Scientists identify 'clean-up' snafu that kills brain cells in Parkinson's disease." ScienceDaily. www.sciencedaily.com/releases/2013/03/130303154850.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Can Watching TV Make You Feel Like A Failure?

Can Watching TV Make You Feel Like A Failure?

Newsy (July 24, 2014) A study by German researchers claims watching TV while you're stressed out can make you feel guilty and like a failure. 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