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 Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>