Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Zebrafish and CHIP help untangle protein misfolding in brain disease

01.11.2005


Keeping the body and mind healthy depends on keeping cells healthy and functioning. This means that cells need a very robust quality-control system to repair or remove damaged or misshapen proteins. Protein handling is especially important in neurons because damage or death of brain cells causes neurological disease.



Researchers in the University of Iowa Roy J. and Lucille A. Carver College of Medicine have identified a protein, called CHIP (C-terminal heat shock protein 70-interacting protein), that links two arms of the quality-control machinery: refolding of misshapen proteins and destruction of proteins that are damaged beyond repair.

"For all kinds of neurodegenerative disease, from Alzheimer’s disease to Huntington’s disease -- which was the focus of our study -- there are problems with protein folding and protein handling," said Henry Paulson, M.D., Ph.D., UI associate professor of neurology and senior author of the study. "The protein CHIP is a key player in that process. Understanding and manipulating this pathway could lead to therapies for these diseases."


Huntington’s disease is a devastating, inherited, neurodegenerative disease that is progressive and always fatal. The disease-causing gene produces a protein that is toxic to certain brain cells, and the subsequent neuronal damage leads to movement disorders, psychiatric disturbances and cognitive decline. The mutated protein contains an abnormally long stretch of a repeated amino acid and is prone to misfold and clump together, forming aggregates.

Working with several models of Huntington’s disease (HD), Paulson and his colleagues found that CHIP could suppress the disease. The study, published in the Oct. 5 issue of the Journal of Neuroscience, demonstrated that CHIP decreased aggregation of the mutant protein and cell death in mouse neurons and in zebrafish. The UI team also found that in mice with only one copy of the CHIP gene, genetically engineered HD progressed more quickly and the mice died earlier than in mice with two copies of the CHIP gene and normal levels of CHIP. These findings indicate that protein quality control is disrupted in HD and also suggest that boosting CHIP ’s action may be a route to potential therapies.

Paulson noted that in addition to showing that CHIP may be a good therapeutic target for neurodegenerative diseases, the study also demonstrates that zebrafish can be a powerful model for human neurodegenerative disease.

Zebrafish, a common tropical fish, have several attributes that make them attractive as lab animals. Unlike mammals, the fish embryos develop very rapidly outside of the mother and the early embryos are transparent allowing researchers to see internal development in the living creatures. Also, zebrafish are easy to manipulate genetically.

"For something that looks so unlike a human being, zebrafish share many genetic similarities including in the brain," Paulson said. "Zebrafish can be a very powerful animal model to study how genes influence and cause disease, including neurodegenerative disorders."

In addition to Paulson, the UI team included Victor Miller, a graduate student and lead author of the study, Rick Nelson, Cynthia Gouvion, Aislinn Williams, Edgardo Rodriguez-Lebron, Ph.D., Scott Harper, Ph.D., Beverly Davidson, Ph.D., the Roy J. Carver Chair in Internal Medicine and UI professor of internal medicine, physiology and biophysics, and neurology, and Michael Rebagliati, Ph.D., UI assistant professor of anatomy and cell biology.

Jennifer Brown | EurekAlert!
Further information:
http://www.uiowa.edu
http://www.uihealthcare.com

More articles from Life Sciences:

nachricht First line of defence against influenza further decoded
21.02.2018 | Helmholtz-Zentrum für Infektionsforschung

nachricht Helping in spite of risk: Ants perform risk-averse sanitary care of infectious nest mates
21.02.2018 | Institute of Science and Technology Austria

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Helping in spite of risk: Ants perform risk-averse sanitary care of infectious nest mates

21.02.2018 | Life Sciences

Fraunhofer ISE Supports Market Development of Solar Thermal Power Plants in the MENA Region

21.02.2018 | Power and Electrical Engineering

A variety of designs for OLED lighting in one easy kit

21.02.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>