Navigation Links
Discovery opens door to new drug options for serious diseases
Date:3/4/2013

CORVALLIS, Ore. Researchers have discovered how oxidative stress can turn to the dark side a cellular protein that's usually benign, and make it become a powerful, unwanted accomplice in neuronal death.

This finding, reported today in Proceedings of the National Academy of Sciences, could ultimately lead to new therapeutic approaches to many of the world's debilitating or fatal diseases.

The research explains how one form of oxidative stress called tyrosine nitration can lead to cell death. Through the common link of inflammation, this may relate to health problems ranging from heart disease to chronic pain, spinal injury, cancer, aging, and amyotrophic lateral sclerosis, or Lou Gehrig's disease.

As part of the work, the scientists also identified a specific "chaperone" protein damaged by oxidants, which is getting activated in this spiral of cellular decline and death. This insight will provide a new approach to design therapeutic drugs.

The findings were published by scientists from the Linus Pauling Institute at Oregon State University; Maria Clara Franco and Alvaro Estevez, now at the University of Central Florida; and researchers from several other institutions. They culminate a decade of work.

"These are very exciting results and could begin a major shift in medicine," said Joseph Beckman.

Beckman is an LPI principal investigator, distinguished professor of biochemistry, and director of the OSU Environmental Health Sciences Center. He also last year received the Discovery Award from the Medical Research Foundation of Oregon, given to the leading medical scientist in the state.

"Preventing this process of tyrosine nitration may protect against a wide range of degenerative diseases," Beckman said. "The study shows that drugs could effectively target oxidatively-damaged proteins."

Scientists have known for decades about the general concept of oxidative damage to cells, resulting in neurodegeneration, inflammation and aging. But the latest findings prove that some molecules in a cell are thousands of times more sensitive to attack.

In this case, heat shock protein 90, or HSP90, helps monitor and chaperone as many as 200 necessary cell functions. But it can acquire a toxic function after nitration of a single tyrosine residue.

"It was difficult to believe that adding one nitro group to one protein will make it toxic enough to kill a motor neuron," Beckman said. "But nitration of HSP90 was shown to activate a pro-inflammatory receptor called P2X7. This begins a dangerous spiral that eventually leads to the death of motor neurons."

The very specificity of this attack, however, is part of what makes the new findings important. Drugs that could prevent or reduce oxidative attack on these most vulnerable sites in a cell might have value against a wide range of diseases.

"Most people think of things like heart disease, cancer, aging, liver disease, even the damage from spinal injury as completely different medical issues," Beckman said. "To the extent they can often be traced back to inflammatory processes that are caused by oxidative attack and cellular damage, they can be more similar than different. It could be possible to develop therapies with value against many seemingly different health problems."

Beckman has spent much of his career studying the causes of amyotrophic lateral sclerosis, and this study suggested the processes outlined in this study might be relevant both to that disease and spinal cord injury.

Key to this research were new methods that allowed researchers to genetically engineer nitrotyrosine into HSP90. This allowed scientists to pin down the exact areas of damage, which may be important in the identification of drugs that could affect this process, the researchers said.


'/>"/>
Contact: Joseph Beckman
joe.beckman@oregonstate.edu
541-737-8867
Oregon State University
Source:Eurekalert

Related medicine news :

1. Scientist awarded $1 million grant to develop tools for hepatitis C treatment discovery
2. Washingtons Life Sciences Discovery Fund awards commercialization grants
3. Discovery could help to develop drugs for organ transplant and cancer patients
4. Feelings of immaturity accompany alcohol misuse into adulthood; discovery could improve treatments
5. H1N1 discovery paves way for universal flu vaccine: UBC research
6. Scientists make breakthrough in bile duct cancer with discovery of new gene mutations
7. Researchers make promising discovery in pursuit of effective lymphoma treatments
8. Discovery suggests new combination therapy strategy for basal-like breast cancers
9. Discovery of Gene May Lead to New Male Contraceptive
10. 5 more pharmaceutical companies join NIH initiative to speed therapeutic discovery
11. Illnesses in Colorado childrens hospital prompts discovery of contaminated alcohol pads
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/11/2016)... , ... February 11, 2016 , ... ... healthcare industry, ranked among the top five firms in the “2015/2016 Best in ... Implementation Support and Staffing. KLAS is a research and insights firm on a ...
(Date:2/11/2016)... FL (PRWEB) , ... February 11, 2016 , ... ... and advocates will discuss how to improve care by making data on heart ... heart disease. The Summit on Transparency and Public Reporting of Pediatric and Congenital ...
(Date:2/11/2016)... , ... February 11, 2016 , ... ... and Reconstructive Surgery, Dallas plastic surgeon , Dr. Rod J. Rohrich, and ... surgery . Dr. Rohrich outlines recommendations for rhinoplasty surgeons when addressing this vital ...
(Date:2/11/2016)... ... February 11, 2016 , ... ... clinical decision support technology, with highly adaptable algorithms, has been updated to help ... has signs and symptoms consistent with Zikas and a travel history to affected ...
(Date:2/11/2016)... ... February 11, 2016 , ... "What holds you ... Ray Clarke poses a question as a challenge for his readers to examine ... in the Being" (published by Partridge Singapore), Clarke explores the subject with more ...
Breaking Medicine News(10 mins):
(Date:2/11/2016)... Feb. 11, 2016   Health 2.0 , the ... health technologies, announced today " 10 Year Global Retrospective ... tech over the past ten years.   ... decade, Health 2.0 has served as the preeminent thought-leader ... with thousands of technologies, companies, innovators, and patient-activists through ...
(Date:2/11/2016)...  AfterPill.com is reporting that this week,s Centers for ... women who are at risk of unintended pregnancy impacts ... raises the risks of unprotected sex in particular.  ... to the Guttmacher Institute, there are 43 million women ... who have sex without the intention of becoming pregnant.  ...
(Date:2/11/2016)... Transformational M&A achieved through NPS and ... --> Transformational M&A achieved through NPS and Dyax acquisitions ... Transformational M&A achieved through NPS and Dyax acquisitions and ... future growth with most robust pipeline in Shire , ... growth with most robust pipeline in Shire , ...
Breaking Medicine Technology: