Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New pathway to Parkinson's and Alzheimer's diseases

30.07.2010
Sanford-Burnham researchers uncover 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. For more information about Sanford-Burnham research, visit http://beaker.sanfordburnham.org.

Original paper: 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. Published online July 30, 2010.

About Sanford-Burnham Medical Research Institute

Sanford-Burnham Medical Research Institute (formerly Burnham Institute for Medical Research) is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Sanford-Burnham, with operations in California and Florida, is one of the fastest-growing research institutes in the country. The Institute ranks among the top independent research institutions nationally for NIH grant funding and among the top organizations worldwide for its research impact. From 1999 – 2009, Sanford-Burnham ranked #1 worldwide among all types of organizations in the fields of biology and biochemistry for the impact of its research publications, defined by citations per publication, according to the Institute for Scientific Information. According to government statistics, Sanford-Burnham ranks #2 nationally among all organizations in capital efficiency of generating patents, defined by the number of patents issued per grant dollars awarded.

Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a nonprofit public benefit corporation.

Josh Baxt | EurekAlert!
Further information:
http://www.sanfordburnham.org

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>