Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research suggests that the production of misshaped proteins ...

07.03.2007
- like the ones associated with neurodegenerative diseases – can affect the immune system

The formation of misshaped proteins - a process suggested to be behind neurodegenerative diseases such as Parkinson’s and Alzheimer’s – can affect an important molecule of the immune system (MHC class I) says a group of Portuguese scientists in an article to be published on the 15th March issue of the "Journal of Immunology".

The researchers have been studying Hereditary Hemochromatosis (HH) – which is also associated with a misshaped/misfolded protein – and discovered that the anomalies in MHC class I molecules observed in some HH patients were linked to a mechanism involved in the elimination of aberrant misfolded proteins. The discovery helps to understand better HH, the most common genetic disease among people of North Europeans ancestry, but also raises important questions on possible immune defects and their role in the many disorders associated with anomalous protein production.

HH is caused by mutations in the HFE gene - which regulates the movement of iron into the cells – and is characterised by excessive absorbance and storage of this metal in the body tissues and organs that can lead, if not treated, to organ failure and even death. Additionally, some HH patients can show anomalies in the numbers of lymphocytes whose development is associated with MHC-I molecules (MHC-I) and which are generally crucial to a proper immune response. Recent research has also shown that HH patients can have abnormal MHC class I molecules what helps to explain the other immune defects observed in these patients.

... more about:
»Almeida »HFE »MHC »MHC-I »Sousa »UPR »abnormal »misfolded »mutated

However, the connection between mutated HFE proteins and abnormal MHC-I molecules has remained a mystery until recent research on a virus of the herpes family suggested that a cellular mechanism used to get rid of misfolded proteins could also affect MHC class I. This observation has led Sergio F. de Almeida, Maria de Sousa and colleagues at Porto University and Lisbon University, Portugal to hypothesise that maybe cellular stress, induced by the production of mutated misfolded HFE proteins, could be behind the MHC-I abnormalities found in HH patients.

In fact, proteins after being produced in the nucleus are delivered to their target sites through a system of “channels” where they also undergo through constant quality controls that, if not passed, result in cellular stress and ultimately in the activation of mechanisms to eliminate the abnormal proteins. The unfolded protein response (UPR) is, like the name indicates, one of such mechanisms specifically responsible for the destruction of misshaped/misfolded proteins. And in the herpes virus study UPR also seemed to be able to affect MHC-I expression.

To test the hypothesis that UPR activation was behind the immune alterations observed in HH patients, de Almeida, de Sousa and colleagues used cells expressing MHC-I molecules but no HFE and genetically manipulated them into expressing normal or mutated (misfolded) HFE proteins. The cells were then analysed for MHC-I expression and UPR activation and compared with non-manipulated cells.

It was found that cells that expressed mutated misfolded HFE proteins showed higher levels of UPR and lower MHC-I expression (due to the production of aberrant MHC-I molecules) in comparison with cells with no HFE or cells with normal HFE proteins. Further supporting the link “misfolded HFE - UPR activation - aberrant MHC-I”, blood cells from HH patients were shown to have UPR activated. Finally, the team of researchers blocked UPR in cells with mutated HFE and this led to increased MHC-I expression further confirming the role of UPR activation behind the MHC-I problems. It was also shown that non-specific UPR activation equally affected MHC-I expression suggesting that this effect may occur in any disease where misfolded proteins are produced and is not specific to HFE

De Almeida, de Sousa and colleagues’ results establish for the first time a link between UPR activation in response to protein misfolding and abnormalities in the immune response. Their work helps the understanding of HH, a disease that affects as many as 1 in 200-300 individuals in the world, but also raises new questions for a range of other disorders, including neurodegenerative illnesses, such as Alzheimer’s, prion’s or Parkinson’s disease, and also type II diabetes and some cancers, all of which are known to be associated with misfolded proteins. The question now is to confirm and understand the possible significance of these alterations in other diseases.

Finally, de Almeida, de Sousa and colleagues’ work also might explain the reason why some viruses induce the production of aberrant misfolded proteins in their infected host as this will affect MHC class I molecules, which are crucial in the immune response against viral infections.

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

Catarina Amorim | alfa
Further information:
http://www.jimmunol.org/cgi/content/abstract/178/6/3612

Further reports about: Almeida HFE MHC MHC-I Sousa UPR abnormal misfolded mutated

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 >>>