Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Potential new treatment for Huntington and Parkinson patients ...

08.03.2006


... can inclusions bodies be good news for neurodegenerative diseases?



A potential new treatment for neurodegenerative disorders, which seems to be able to reduce the toxic protein aggregates characteristic of many of these diseases, is published online this week in the journal Proceedings of the National Academy of Sciences. Since it is believed that in most neurodegenerative disorders, like Parkinson and Huntington’s disease (PD and HD respectively), abnormal protein aggregates are major culprits associated with neurodegeneration, this research may have important implications for the lives of thousands of neurodegenerative patients all over the world.

Parkinson’s and Huntington’s diseases are incurable devastating brain disorders that result from the death of brain cells associated with muscle control. Both illnesses, like many other neurodegenerative diseases, result from the formation of misshaped/incorrectly folded versions of normal proteins (all proteins have a specific shape/folding associated with their normal function) that tend to clump together leading to the death of the cells in the neighbourhood.


But the formation of these abnormal proteins is usually not a problem as two effective mechanisms exist to eliminate them: proteasomes, which are multi-protein complexes capable of digesting/cutting the toxic proteins into small pieces to be easily disposed and molecular chaperones, proteins capable of assisting other proteins to “move” into their correct shape/fold. In the cases where abnormal proteins are allowed to accumulate, as it happens in many neurodegenerative diseases, it is believed that these protective systems are malfunctioning. The fact that HD patients are known to have problems with faulty proteasomes supports this hypothesis.

Furthermore, cells with high accumulation of misshaped proteins, including those from PD and HD patients, can also present a cellular structure called inclusion body, which is known to accumulate high quantities of the altered aggregated protein. The role of these inclusions is not clear, and while for a long time they were believed to be toxic and part of the disease process, in recent years, this has been challenged and some researchers now believe that inclusion bodies (also called inclusions) might have a role eliminating the aggregates of toxic proteins. The fact that inclusion bodies are known to contain high quantities of proteasomes further supports this hypothesis. Nevertheless, research in therapies for neurodegenerative diseases seems to continue orientated towards drugs capable of diminish these cellular structures

But Ruth A. Bodner, Tiago Fleming Outeiro, a Portuguese scientist, Aleksey G. Kazantsev and colleagues from the Center for Cancer Research, Massachusetts Institute of Technology, Cambridge and the Mass General Institute for Neurodegenerative Disease, Massachusetts General Hospital, and Harvard Medical School, US had a different idea.

In fact, although much research has been done on compounds capable of diminish the number of inclusions in cells with neurodegenerative mechanisms so far the results have been inconclusive. This observation, together with the emerging believe that inclusions might actually be involved in cells’ protection, made Bodner, Outeiro, Kazantsev and colleagues decide to look instead at substances known to increase the number of inclusions, analysing their effect on neurodegenerative mechanisms. For that they used cellular models of PD and HD consisting of cells, growing in laboratory, which are induced to produce toxic quantities of the protein associated with each of the diseases.

As expected, Bodner, Outeiro, Kazantsev and colleagues found that the compounds that increased the amount of misshaped protein also induced the formation of cellular inclusions. But, more interestingly, was the fact that among those substances that increased inclusions’ numbers, a few were able to revert (and very efficiently) some of the harmful effects induced by the toxic aggregates of misshaped proteins.

In fact, in the cellular model of HD some of the tested substances were able to recover proteasome function - which is crucial to eliminate abnormal proteins in the cells and is known to be defective in HD – while in the PD model the tested substances were capable of diminish the toxicity of the misshaped proteins associated with disease and, in consequence, also cellular death. Furthermore, these beneficial effects correlated directly with the number of inclusions formed, further supporting the idea that inclusions bodies are not necessarily part of the disease, but instead a coing mechanism.

Bodner, Outeiro, Kazantsev and colleagues also had two other very interesting findings. Firstly, the remarkable effectiveness of the substances tested - the most effective compound was able to recover up to 39% of proteasome function in the HD model, while reducing 46% the toxicity associated with the protein aggregates in the model of PD – what raises hopes that these substances might become important new drugs. Secondly, the identification of specific atoms in the tested substances, that, when changed, reduced drastically the substances’ effectiveness. This last observation raises the possibility that different changes in the already identified areas, might, instead, be able to increase even more the effectiveness of the potential drugs.

At the moment the treatments available for neurodegenerative patients are only able to treat the individual symptoms but not the disease. What Bodner, Outeiro, Kazantsev and colleagues’ research might mean is that one day we will be able to delay, or even revert, disease symptoms, giving patients the possibility of enjoying for longer the pleasure of a normal life. Although much more research is necessary in order to confirm these results, Bodner, Outeiro, Kazantsev and colleagues’ new work is undoubtedly exciting news for neurodegenerative patients all over the world.

Piece researched and written by: Catarina Amorim ( catarina.amorim@linacre.ox.ac.uk)

Catarina Amorim | alfa
Further information:
http://www.pnas.org/cgi/content/abstract/0511256103v1

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 >>>