Featured Research

from universities, journals, and other organizations

Faulty clean-up process may be key event in Huntington's disease

Date:
April 25, 2010
Source:
Albert Einstein College of Medicine
Summary:
In a step towards a possible treatment for Huntington's disease, scientists have shown for the first time that the accumulation of a mutated protein may explain damaging cellular behavior in Huntington's disease.

In a normal cell (above), a membranous structure known as an autophagosome collects cellular debris and delivers it to an enzyme-filled bag called a lysosome for digestion. But in Huntington’s disease (below), defective huntingtin proteins (in purple) stick to the inner layer of the autophagosome, preventing it from collecting debris. The autophagosome arrives empty at the lysosome, allowing debris to accumulate to toxic levels inside the cell.
Credit: Image courtesy of Albert Einstein College of Medicine

In a step towards a possible treatment for Huntington's disease, scientists at Albert Einstein College of Medicine of Yeshiva University have shown for the first time that the accumulation of a mutated protein may explain damaging cellular behavior in Huntington's disease. Their research is described in the April 11 online edition of Nature Neuroscience.

Huntington's disease, which afflicted the folksinger Woody Guthrie, is a fatal, inherited neurodegenerative disorder. While subtle personality changes and diminished physical skills may occur early in the disease, it typically becomes noticeable during middle age. Later problems include dementia and chorea -- jerky movements that are random and uncontrollable.

Huntington's disease results from a gene mutation that leads to a defective form of the huntingtin protein. The mutation is dominant, meaning that a child of an affected parent has a 50 percent chance of inheriting Huntington's. And since the defective protein is present in all of a person's cells, the disease causes problems in the brain and throughout the body.

"Studies have shown that Huntington's disease occurs in part because the mutated huntingtin protein accumulates within cells and is toxic to them," said Ana Maria Cuervo, M.D., Ph.D., professor of developmental and molecular biology, of anatomy and structural biology, and of medicine at Einstein and senior author of the Nature Neuroscience study. "In our investigation of how the accumulating huntingtin protein affects the functioning of cells, we found that it interferes with the cells' ability to digest and recycle their contents."

All cells rely on several different mechanisms to break down "old" proteins and other components and recycle them. Collectively known as autophagy (literally, "self-eating"), these processes keep cells clean and uncluttered and provide them with replacement parts that will function better.

Dr. Cuervo and her team had previously shown that a glitch in autophagy may trigger Parkinson's disease by allowing a toxic protein to accumulate. She suspected that something similar was going on in Huntington's disease. After studying two mouse models of Huntington's disease as well as lymphoblasts (white cells) from people with the disease, she and her team found that the mutated huntingtin protein was sabotaging the cell's garbage-collecting efforts.

One mechanism for cleaning up cells involves forming a membrane around the protein or other cellular structure requiring removal. These "garbage bags" (more formally known as autophagosomes) then travel to enzyme-filled sacs known as lysosomes that fuse with the bags and digest their cargo. But the clean-up efforts go awry in Huntington's disease.

Dr. Cuervo and her team found that the defective huntingtin proteins stick to the inner layer of autophagosomes, preventing them from gathering garbage. The result: Autophagosomes arrive empty at the lysosomes; and cellular components that should be recycled instead accumulate, causing toxicity that probably contributes to cell death.

This finding, Dr. Cuervo noted, shows that activating the lysosomes of cells -- one of the proposed treatments for Huntington's disease -- won't do any good.

"It doesn't matter how active your lysosomes are if they're not going to receive any cellular components to digest," she said. "Instead, we should focus on treatments to help autophagosomes recognize intracellular garbage, perhaps by minimizing their contact with the defective huntingtin protein. By enhancing the clearance of cellular debris, we may be able to keep Huntington's patients free of symptoms for a longer time."


Story Source:

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


Journal Reference:

  1. Martinez-Vicente et al. Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease. Nature Neuroscience, 2010; DOI: 10.1038/nn.2528

Cite This Page:

Albert Einstein College of Medicine. "Faulty clean-up process may be key event in Huntington's disease." ScienceDaily. ScienceDaily, 25 April 2010. <www.sciencedaily.com/releases/2010/04/100411143355.htm>.
Albert Einstein College of Medicine. (2010, April 25). Faulty clean-up process may be key event in Huntington's disease. ScienceDaily. Retrieved September 30, 2014 from www.sciencedaily.com/releases/2010/04/100411143355.htm
Albert Einstein College of Medicine. "Faulty clean-up process may be key event in Huntington's disease." ScienceDaily. www.sciencedaily.com/releases/2010/04/100411143355.htm (accessed September 30, 2014).

Share This



More Health & Medicine News

Tuesday, September 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How 'Yes Means Yes' Defines Sexual Assault

How 'Yes Means Yes' Defines Sexual Assault

Newsy (Sep. 29, 2014) Aimed at reducing sexual assaults on college campuses, California has adopted a new law changing the standard of consent for sexual activity. Video provided by Newsy
Powered by NewsLook.com
Scientists May Have Found An Early Sign Of Pancreatic Cancer

Scientists May Have Found An Early Sign Of Pancreatic Cancer

Newsy (Sep. 29, 2014) Researchers looked at 1,500 blood samples and determined people who developed pancreatic cancer had more branched chain amino acids. Video provided by Newsy
Powered by NewsLook.com
Colo. Doctors See Cluster of Enterovirus Cases

Colo. Doctors See Cluster of Enterovirus Cases

AP (Sep. 29, 2014) Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
Powered by NewsLook.com
Dr.'s Unsure of Cause of Fast-Spreading Virus

Dr.'s Unsure of Cause of Fast-Spreading Virus

AP (Sep. 29, 2014) Doctors at the Children's Hospital of Colorado say they have treated over 4,000 children with serious respiratory illnesses since August. Nine of the patients have shown distinct neurological symptoms, including limb weakness. (Sept. 29) Video provided by AP
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