Navigation Links
UCLA scientists find molecular switch to prevent Huntington's disease in mice
Date:12/24/2009

UCLA scientists have identified a molecular switch that prevents Huntington's disease from developing in mice. Published in the Dec. 24 edition of the journal Neuron, the discovery suggests a new approach to treating the genetic disorder, which ultimately leads to death in as little as 10 years.

Affecting one out of every 10,000 Americans, Huntington's progressively deprives patients of their ability to walk, speak, think clearly and swallow. People who inherit the disorder don't show symptoms until mid-life, after many have had children and unknowingly passed on the disease. Currently, there is no effective treatment to prevent the onset or slow the progression of the disease.

Huntington's is caused by a mutation in the polyglutamine (polyQ) region of a very large protein called huntingtin. Because huntingtin is found everywhere in the body, it is a challenge to study, and the function and mechanism behind the mutant protein still remain elusive.

"It's unclear how the mutant protein causes age-related and progressive loss of brain cells in patients with Huntington's disease," said senior study author X. William Yang, associate professor of psychiatry and biobehavioral sciences at the Semel Institute of Neuroscience and Human Behavior at UCLA. "We explored whether regions of the protein besides the polyQ mutation play a role in the development of the disorder."

Collaborators Joan Steffan and Leslie Thompson, of the University of California, Irvine, showed that two amino acids near the beginning of the huntingtin protein can be modified by a chemical process called phosphorylation, which cells use to control protein function after the proteins have been made.

To test whether phosphorylation could influence Huntington's disease in a living animal, Yang's laboratory generated two mouse models to carry the polyQ HD mutation and modified the two amino acids in two different ways one to mimic phosphorylation, the other to prevent it.

The researchers found that preventing phosphorylation caused the mice to develop symptoms suggestive of Huntington's disease in humans. Mimicking phosphorylation, however, did not cause the disorder.

These results in mice have striking parallels to experiments performed by collaborator Ron Wetzel, of the University of Pittsburgh, who found that mimicking phosphorylation of a toxic fragment of mutant huntingtin reduces the protein's tendency to form clumps.

A separate UC Irvine study by Steffan and Thompson also suggests that phosphorylation of mutant huntingtin may help cells dispose of the toxic form of mutant huntingtin. Combined, these studies suggest new directions of research to understand the roles of huntingtin misfolding, clumping and clearance in the disease mechanism.

"Our study identified a critical molecular switch which lies next to the polyQ mutation in the huntingtin protein," Yang said. "We were surprised to find that subtle modification of only two amino acids in this very large protein can prevent the onset of disease. This finding suggests an exciting new avenue to develop therapeutics for Huntington's disease."


'/>"/>

Contact: Elaine Schmidt Haber
ehaber@mednet.ucla.edu
310-794-2272
University of California - Los Angeles
Source:Eurekalert

Related biology news :

1. Turtles Christmas journey tracked by scientists
2. Scientists isolate new antifreeze molecule in Alaska beetle
3. Scientists use nanosensors for first time to measure cancer biomarkers in blood
4. Scripps Research scientists crack mystery of proteins dual function
5. Scientists identify natural anti-cancer defenses
6. Princeton scientists find way to catalog all that goes wrong in a cancer cell
7. The pitch of blue whale songs is declining around the world, scientists discover
8. Stand Up to Cancer funds high-risk/high-reward cancer research by 13 young scientists
9. Scientists discover gene module underlying atherosclerosis development
10. Scientists think killer petunias should join the ranks of carnivorous plants
11. Scientists gain new understanding of disease-causing bacteria
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/8/2017)... 7, 2017 Report Highlights The ... from $8.3 billion in 2016 at a compound annual ... Report Includes - An overview of the global ... with data from 2015 and 2016, and projections of ... of the market on the basis of product type, ...
(Date:2/3/2017)... 3, 2017  Texas Biomedical Research Institute announced that its ... Schlesinger as the Institute,s new President and CEO. Dr. ... 31, 2017. He is currently the Chair of the Department ... for Microbial Interface Biology at Ohio State University. ... President and CEO of Texas Biomed," said Dr. James ...
(Date:2/1/2017)... 2017 IDTechEx Research, a leading provider of ... the availability of a new report, Sensors for Robotics: Technologies, ... Reading ... ... Source: IDTechEx Report "Sensors for Robotics: Technologies, Markets and Forecasts 2017-2027: ...
Breaking Biology News(10 mins):
(Date:2/24/2017)... BEIJING, Feb. 23, 2017 China Biologic Products, Inc. ... integrated plasma-based biopharmaceutical company in China, today announced its financial ... Fourth Quarter 2016 Financial Highlights ... increased by 21.7% in RMB terms, or increased by 13.6% ... the same quarter of 2015. Gross profit ...
(Date:2/24/2017)... -- OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing ... Leader event to highlight new clinical data that will ... the upcoming 2017 ASCO-SITC Immuno-Oncology Symposium and the Company,s ... in-person and via live webcast on Tuesday, February 28 ... the Lotte New York Palace Hotel in ...
(Date:2/23/2017)... Calif., Feb. 23, 2017 ... dollars, except per share data, unaudited)Three Months Ended December ... BioMarin Revenue $     ... 22832%$ 1,117$   89026%Aldurazyme Net Product Revenue ... 906538%34823946%Naglazyme Net Product Revenue  ...
(Date:2/23/2017)... /PRNewswire/ - The Fight Against Cancer Innovation Trust (FACIT) ... pleased to report that Fusion Pharmaceuticals Inc. (Fusion) has ... Johnson Innovation – JJDC, Inc. (JJDC) as the lead ... Biotechnology Partners, and Genesys Capital, as well as founding ... ...
Breaking Biology Technology: