Navigation Links
Molecular trigger for Huntington's disease found

Researchers have discovered a key regulatory molecule whose overactivation by the abnormal protein produced in Huntington's disease (HD) causes the central pathologies of the disease. The abnormal HD protein activates the regulatory protein called p53, which in turn switches on a host of other genes. This abnormal gene activation damages the cells' power plants, called the mitochondria, and kills brain cells.

The researchers also speculated that disturbances in p53 may also play a role in some forms of Parkinson's disease and amyotrophic lateral sclerosis, or Lou Gehrig's disease.

Ironically, p53 is the same regulatory protein that is inactivated in a large fraction of cancers. This inactivation allows abnormal cancer cells to escape the cell's protective "suicide program" that would normally kill them. The researchers theorize that the lower incidence of cancer in HD patients could be caused by the protective effect of overactive p53.

In the July 7, 2005, issue of Neuron, Akira Sawa and colleagues at Johns Hopkins University School of Medicine reported experiments ranging from molecular studies in cultured brain cells to analysis of the brains of human HD patients that demonstrated the central role of p53 in the pathologies of HD.

Their studies with cell cultures showed that the abnormal HD protein selectively binds to p53 and increases its level in cells. They noted that the brains of patients with HD also show substantial increases in the p53 protein, with the highest levels in cases with the most extensive pathology.

The researchers' experiments also revealed that this p53 increase causes an overactivation in the genes regulated by p53, which is called a "nuclear transcription factor" because it regulates the transcription of its target genes in cell nuclei.

In studies of cell cultures and of mice engineered to have HD, the researchers found that the p53 increase causes malfunctions in mitochondria. What's more, the y found that this p53 increase induced by the abnormal HD protein greatly increases cell death.

The researchers also found effects of the abnormality in p53 in whole animals. They found that deleting p53 suppresses damage to neurons in the eye of fruit flies engineered to have the abnormal HD protein. And in mice with the abnormal protein, knocking out p53 corrects behavioral abnormalities that the mice otherwise display. These behaviors include abnormal reflexes such as an inhibited startle response to loud noise, which is also present in human HD patients.

"In summary, our study establishes a specific role for p53 in HD," concluded Sawa and colleagues. "As p53 is a nuclear transcription factor that regulates various mitochondrial genes and insofar as mitochondrial dysfunction appears important in HD, our findings provide a molecular mechanism linking disturbances of nuclei and mitochondria in HD."

Byoung-Il Bae, Shuichi Igarashi, Masahiro Fujimuro, Nishant Agrawal, Yoichi Taya, S. Diane Hayward, Timothy H Moran, Christopher A Ross, Solomon H Snyder, Akira Sawa: "p53 Mediates Cellular Dysfunction and Behavioral Abnormalities in Huntington's Disease" DOI 10.1016/j.neuron.2005.06.005 Publishing in Neuron, Volume 47, July 7, 2005, pages 29-41.


Source:Cell Press

Related biology news :

1. Molecular biology fills gaps in knowledge of bat evolution
2. Molecular machine may lead to new drugs to combat human diseases
3. Molecular Motors Cooperate In Moving Cellular Cargo, Study Shows
4. Molecular models advance the fight against malaria
5. Molecular fossils uncover link between viruses and the immune system
6. Molecular thermometers on skin cells detect heat and camphor
7. Molecular messengers perform a crucial role in the ability of injured nerve cells to heal themselves
8. Molecular steps involved in the creation of gene-silencing microRNAs identified
9. Molecular miners find pain relief drugs from the sea
10. Molecular mechanism of feather formation found
11. Molecular Partners Required For Appropriate Neuronal Gene Repression
Post Your Comments:

(Date:6/21/2016)... 21, 2016 NuData Security announced today that ... of principal product architect and that Jon ... customer development. Both will report directly to ... moves reflect NuData,s strategic growth in its product ... customer demand and customer focus values. ...
(Date:6/15/2016)... New York , June 15, 2016 /PRNewswire/ ... a new market report titled "Gesture Recognition Market by ... and Forecast, 2016 - 2024". According to the report, ... USD 11.60 billion in 2015 and is estimated ... reach USD 48.56 billion by 2024.  ...
(Date:6/7/2016)... 7, 2016  Syngrafii Inc. and San Antonio ... that includes integrating Syngrafii,s patented LongPen™ eSignature "Wet" ... collaboration will result in greater convenience for SACU ... while maintaining existing document workflow and compliance requirements. ... Highlights: ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... June 23, 2016 /PRNewswire/ - FACIT has announced ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" ... commercialization of a portfolio of first-in-class WDR5 inhibitors ... such as WDR5 represent an exciting class of ... precision medicine for cancer patients. Substantial advances have ...
(Date:6/23/2016)... YORK , June, 23, 2016  The Biodesign ... to envision new ways to harness living systems and ... Modern Art (MoMA) in New York City ... than 130 participating students, showcased projects at MoMA,s Celeste ... Paola Antonelli , MoMA,s senior curator of architecture ...
(Date:6/23/2016)... 2016 Apellis Pharmaceuticals, Inc. today announced ... of its complement C3 inhibitor, APL-2. The trials ... dose studies designed to assess the safety, tolerability, ... in healthy adult volunteers. Forty subjects ... single dose (ranging from 45 to 1,440mg) or ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... regulatory and technical consulting, provides a free webinar on Performing Quality ... 13, 2016 at 12pm CT at no charge. , Incomplete investigations are still ...
Breaking Biology Technology: