Featured Research

from universities, journals, and other organizations

New pathway to Parkinson's and Alzheimer's diseases

Date:
July 30, 2010
Source:
Sanford-Burnham Medical Research Institute
Summary:
Researchers have uncovered new clues about the cause of brain cell death in neurodegenerative disorders such as Parkinson's, Alzheimer's and Huntington's diseases.

Although their genetic underpinnings differ, Alzheimer's disease, Parkinson's disease and Huntington's disease are all characterized by the untimely death of brain cells. What triggers cell death in the brain?

According to a new study published by researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) in the July 30 issue of Molecular Cell, the answer in some cases is the untimely transfer of a gaseous molecule (known as nitric oxide, or NO) from one protein to another.

"We and other researchers have shown that NO and related molecules can contribute to either nerve cell death or nerve cell survival. However, these new findings reveal that NO can actually jump from one protein to another in molecular pathways that lead to cellular suicide," explained Stuart A. Lipton, M.D., Ph.D., senior author of the study and director of the Del E. Web Center for Neuroscience, Aging and Stem Cell Research at Sanford-Burnham. "Now that we have this molecular clue to the cause of nerve cell death in Parkinson's, Alzheimer's, and Huntington's diseases, we can figure out how to use it to better diagnose and treat these diseases." Dr. Lipton is also a Harvard-trained neurologist who sees many of these patients in his own clinical practice.

In this study, Dr. Lipton and his colleagues, led by Tomohiro Nakamura, Ph.D., found that NO-like molecules are transferred from caspases, proteins that normally initiate cell death, to XIAP, a protein that normally inhibits cell death. In other words, caspases pass NO to XIAP like a 'hot potato.' This process occurs by a chemical reaction known as transnitrosylation. When XIAP is left holding NO, the result is a double whammy for brain cells, since cells are programmed to self-destruct when either XIAP has NO attached to it or when caspases don't. Hence, both brain cell-destroying events occur at the same time. The researchers then found that XIAP holding the NO 'hot potato' was much more common in brains of human patients with neurodegenerative diseases than in normal brains, solidifying their suspicion that this protein modification leads to cell damage.

To calculate which protein is more likely to end up with the NO 'hot potato,' caspases or XIAP, the researchers created a new version of the Nernst equation -- a 19th century mathematical equation taught in every general chemistry class. This power of prediction might allow doctors to diagnose neurodegenerative disorders like Parkinson's or Alzheimer's disease earlier.

"We are currently analyzing cerebrospinal fluid and brain tissue from Parkinson's, Alzheimer's and other patients to determine if we can use the NO-tagged proteins as biomarkers for the disease," Dr. Lipton said.

In order to develop therapies to treat Parkinson's, Alzheimer's and Huntington's diseases based on their new findings, Dr. Lipton's laboratory is also applying the robotic technology in Sanford-Burnham's Conrad Prebys Center for Chemical Genomics to screen thousands of chemicals for potential drugs that prevent the aberrant or excessive transfer of NO from one protein to another, and thus to prevent nerve cell injury and death.

This study was supported by grants from the National Institutes of Health (NIH) and the San Diego chapter of the American Parkinson's Disease Association.


Story Source:

The above story is based on materials provided by Sanford-Burnham Medical Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Nakamura T, Wang L, Wong CCL, Scott FL, Eckelman BP, Han X, Tzitzilonis C, Meng F, Gu Z, Holland EA, Clemente AJ, Okamoto S, Salvesen GS, Riek R, Yates JR 3rd, Lipton SA. Transnitrosylation of XIAP regulates caspase-dependent neuronal cell death. Molecular Cell, July 30, 2010

Cite This Page:

Sanford-Burnham Medical Research Institute. "New pathway to Parkinson's and Alzheimer's diseases." ScienceDaily. ScienceDaily, 30 July 2010. <www.sciencedaily.com/releases/2010/07/100729133436.htm>.
Sanford-Burnham Medical Research Institute. (2010, July 30). New pathway to Parkinson's and Alzheimer's diseases. ScienceDaily. Retrieved April 20, 2014 from www.sciencedaily.com/releases/2010/07/100729133436.htm
Sanford-Burnham Medical Research Institute. "New pathway to Parkinson's and Alzheimer's diseases." ScienceDaily. www.sciencedaily.com/releases/2010/07/100729133436.htm (accessed April 20, 2014).

Share This



More Health & Medicine News

Sunday, April 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Nine-Month-Old Baby Can't Open His Mouth

Nine-Month-Old Baby Can't Open His Mouth

Newsy (Apr. 19, 2014) Nine-month-old Wyatt Scott was born with a rare disorder called congenital trismus, which prevents him from opening his mouth. Video provided by Newsy
Powered by NewsLook.com
'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. 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