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 Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

nachricht Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

NASA's Fermi catches gamma-ray flashes from tropical storms

25.04.2017 | Physics and Astronomy

Researchers invent process to make sustainable rubber, plastics

25.04.2017 | Materials Sciences

Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017

25.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>