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. http://www.neuron.org/


'"/>

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:
*Name:
*Comment:
*Email:


(Date:6/22/2016)... ANGELES , June 22, 2016 /PRNewswire/ ... identity management and verification solutions, has partnered ... edge software solutions for Visitor Management, Self-Service ... provides products that add functional enhancements ... partnership provides corporations and venues with an ...
(Date:6/16/2016)... , June 16, 2016 ... size is expected to reach USD 1.83 billion ... Grand View Research, Inc. Technological proliferation and increasing ... applications are expected to drive the market growth. ... , The development of advanced multimodal ...
(Date:6/7/2016)...  Syngrafii Inc. and San Antonio Credit Union ... integrating Syngrafii,s patented LongPen™ eSignature "Wet" solution into ... result in greater convenience for SACU members and ... existing document workflow and compliance requirements. ... Highlights: ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... -- Liquid Biotech USA , Inc. ... Research Agreement with The University of Pennsylvania ("PENN") ... patients.  The funding will be used to assess ... outcomes in cancer patients undergoing a variety of ... to support the design of a therapeutic, decision-making ...
(Date:6/24/2016)... , ... June 24, 2016 , ... While the majority ... as the Cary 5000 and the 6000i models are higher end machines that use ... height of the spectrophotometer’s light beam from the bottom of the cuvette holder. ...
(Date:6/23/2016)... 2016   Boston Biomedical , an industry ... to target cancer stemness pathways, announced that its ... Drug Designation from the U.S. Food and Drug ... including gastroesophageal junction (GEJ) cancer. Napabucasin is an ... cancer stemness pathways by targeting STAT3, and is ...
(Date:6/23/2016)... MA (PRWEB) , ... June 23, 2016 , ... ... Peel Plate® YM (Yeast and Mold) microbial test has received AOAC Research Institute ... platform of microbial tests introduced last year,” stated Bob Salter, Vice President of ...
Breaking Biology Technology: