Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Antibiotic rifampicin shows promise for fighting Parkinson’s disease in lab tests

30.11.2004


Researchers at the University of California, Santa Cruz, have shown that rifampicin, an antibiotic used to treat leprosy and tuberculosis, can prevent the formation of protein fibrils associated with the death of brain cells in people with Parkinson’s disease. The drug also dissolved existing fibrils in laboratory tests.



The researchers studied the effects of rifampicin in test tube experiments and are currently doing studies with cell cultures and mice to see if the same effects occur in living cells. Although these are just the first steps along the path toward clinical studies in humans, the findings suggest that rifampicin and related compounds might be effective in preventing fibril formation and associated neurological damage in patients with Parkinson’s disease, said Anthony Fink, professor of chemistry and biochemistry at UCSC. "Clearly, more work is needed to determine if this would work therapeutically, but if it does it would probably be most useful as a prophylactic therapy used in the early stages of the disease before there is general neurological damage," Fink said.

The research was carried out by a team of scientists in Fink’s lab, including postdoctoral researchers Jie Li, Min Zhu, and Sudha Rajamani and research associate Vladimir Uversky. Li is first author of a paper describing their results in the November issue of the journal Chemistry and Biology, which is mailed and published online on November 29.


Aggregation of the protein known as alpha-synuclein into insoluble fibrils is thought to be a critical step in the development of Parkinson’s disease, a progressive movement disorder resulting from the death of nerve cells in the brain that produce the neurotransmitter dopamine. Deposits called Lewy bodies, composed mostly of alpha-synuclein fibrils, appear in affected nerve cells, but the connection between the fibrils and cell death remains controversial, Fink said. "There are two schools of thought: One is that the fibrils themselves are toxic, and the other is that smaller precursors of the fibrils formed earlier in the process are toxic and cause the neurons to die," he said.

Fink’s group found that rifampicin stabilized alpha-synuclein in a soluble form, both as single molecules and in small, soluble clumps of the protein, thereby preventing the formation of fibrils. Furthermore, addition of the drug to already-formed fibrils of alpha-synuclein resulted in disaggregation of the fibrils into soluble clumps and single molecules. Fink noted that preliminary data from experiments in cell cultures and in mice indicate that the soluble clumps of alpha-synuclein formed in the presence of rifampicin are nontoxic. "The disaggregation of existing fibrils is probably the most interesting and novel finding in this study. If it works in people, that would really open up the possibility of stopping the progression of Parkinson’s disease when it is first diagnosed," he said.

The researchers used several different techniques to study the mechanism underlying rifampicin’s effects on alpha-synuclein. They found that the drug and its breakdown products bind tightly to alpha-synuclein, possibly even reacting with it to form a stable compound. Their findings with rifampicin are very similar to previous research in Fink’s lab with the compound baicalein, a flavonoid that also inhibits fibril formation and disaggregates existing fibrils of alpha-synuclein. Those results were published in June in the Journal of Biological Chemistry. "We wanted to look at rifampicin because it is an already-approved drug that is similar to baicalein in key parts of its molecular structure," Fink said.

Research in other laboratories has found that rifampicin may also prevent the formation of the protein deposits that characterize Alzheimer’s disease, which are composed of a different protein from alpha-synuclein. In addition, epidemiological studies of leprosy patients have indicated that patients treated for several years with rifampicin had a lower probability of developing senile dementia. "Dementia is associated with Alzheimer’s disease and with about one third of patients with Parkinson’s disease. But no studies have looked specifically at Parkinson’s disease in people taking this drug," Fink said.

Tim Stephens | EurekAlert!
Further information:
http://www.ucsc.edu

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>