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 How cancer metastasis happens: Researchers reveal a key mechanism
19.01.2018 | Weill Cornell Medicine

nachricht Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center

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: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Thanks for the memory: NIST takes a deep look at memristors

22.01.2018 | Materials Sciences

Radioactivity from oil and gas wastewater persists in Pennsylvania stream sediments

22.01.2018 | Earth Sciences

Saarland University bioinformaticians compute gene sequences inherited from each parent

22.01.2018 | Life Sciences

VideoLinks Wissenschaft & Forschung
Overview of more VideoLinks >>>