Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Two-Fisted Assault on Dopamine Transport System May Be Foundation of Parkinson’s Disease

06.12.2004


Protecting microtubule "highways" may lead to novel therapies, study shows



Parkinson’s disease may be caused by an environmental-genetic double whammy on the neurons that produce dopamine, the neurotransmitter that controls body movement, a new study has shown.

Researchers at the University at Buffalo, using cultures of rat neurons, have shown that the presence of mutated parkin genes, combined with the toxic effects of the chemical rotenone, results in a cascade of highly toxic free radicals, the destruction of microtubules that transport dopamine to the brain’s movement center, and eventual death of the dopamine-producing neuron.


"This study shows how an environmental toxin and a gene linked to Parkinson’s disease affect the survival of dopamine neurons by dueling on a common molecular target -- microtubules -- that are critical for the survival of dopamine-producing neurons," said Jian Feng, Ph.D., assistant professor of physiology and biophysics in UB School of Medicine and Biomedical Sciences and senior author. "Based on these findings, we have identified several ways to stabilize microtubules against the onslaught of rotenone. These results ultimately may lead to novel therapies for Parkinson’s disease."

Results of the research will be presented Dec. 5 at the American Society for Cell Biology meeting in Washington D.C.

Researchers who study Parkinson’s disease know that persons with a mutation in the parkin gene are at risk for the disease, and that exposure to agricultural chemicals, including rotenone, cause Parkinson’s-like symptoms in animals. In addition, long-term epidemiological studies of Parkinson’s disease patients have shown a strong link between exposure to pesticides/herbicides and increased risk of developing the disease, Feng noted.

Earlier research by several groups has shown that rotenone destroys only neurons that produce dopamine, while largely sparing neurons that produce other neurotransmitters. Dr. Feng’s laboratory set out to answer the questions "Why?" and "How?" By studying the effects of rotenone on rat neurons, they discovered that one of the targets of the pesticide was microtubules – intracellular highways for transporting various chemicals such as dopamine to the brain area that controls body movement. Normally the enzyme parkin would protect the neuron from rotenone’s assault on microtubules, Feng said.

"When microtubules are broken down by rotenone, the disassociated protein building blocks, called tubulin, are left behind," he said. "These tubulins are probably misfolded proteins. Left unattended, they could interfere with the normal assembly of microtubules. Based on our previous work that parkin marks this ’old’ tubulin for rapid degradation, we theorize that parkin may thus prevent this interference."

Mutated parkin loses this protective ability, however, allowing rotenone to do its damage unchecked. Feng and colleagues showed that rotenone damages the microtubules, which prevents dopamine from reaching the brain’s movement center, causing a back-up in the dopamine transport system. Meanwhile, the backed-up dopamine accumulates in the neuron’s cytoplasm and breaks down, causing a release of toxic free radicals, which destroy the neuron.

Additional researchers on the study were Yong Ren, Ph.D., Wenhua Liu, Ph.D. and Houbo Jiang, Ph.D., postdoctoral associates in the UB Department of Physiology and Biophysics.

The study was funded by a grant from the National Institute of Health.

The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York.

Lois Bakjer | EurekAlert!
Further information:
http://www.buffalo.edu

More articles from Health and Medicine:

nachricht NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

nachricht High speed video recording precisely measures blood cell velocity
15.11.2017 | ITMO University

All articles from Health and Medicine >>>

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

Heavy nitrogen molecules reveal planetary-scale tug-of-war

20.11.2017 | Earth Sciences

Taking a spin on plasma space tornadoes with NASA observations

20.11.2017 | Physics and Astronomy

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>