Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Study using robotic microscope shows how mutant Huntington’s protein affects neurons


Using a specially designed robotic microscope to study cultured cells, researchers have found evidence that abnormal protein clumps called inclusion bodies in neurons from people with Huntington’s disease (HD) prevent cell death. The finding helps to resolve a longstanding debate about the role of these inclusion bodies in HD and other disorders and may help investigators find effective treatments for these diseases. The study was funded primarily by the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and appears in the October 14, 2004, issue of Nature.*

Inclusion bodies are common to many neurodegenerative disorders, including HD, Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis (ALS). The role of inclusion bodies in these diseases has long been controversial. Some studies suggest that they may be a critical part of the disease process, while others indicate that they may help protect the cells from toxic proteins or that they are merely bystanders in the disease process.

One problem in identifying how inclusion bodies influence disease is that researchers have been unable to track changes in individual neurons over time. "It was like viewing pictures of a football game and trying to imagine the score," says Steven Finkbeiner, M.D., Ph.D., of the Gladstone Institute of Neurological Disease and the University of California, San Francisco. "Much was happening that we couldn’t see."

To overcome this problem, Dr. Finkbeiner and his colleagues wrote a computer program that allows a microscope to match images in a culture dish to images it has stored and to manipulate its controls to look at the same neurons over and over again - like time-lapse photography. This allowed the investigators to follow changes in a single neuron or a group of neurons over a period of days. They used this automated microscope to study neurons that contained a version of the huntingtin protein that causes HD. The huntingtin was fused to green fluorescent protein, a widely used marker that allows researchers to see where proteins accumulate.

Many neurons with the mutated HD gene died without forming inclusion bodies, the researchers found. The formation of inclusion bodies actually prolonged neurons’ survival and lowered their overall risk of death. The rate of cell death was higher in neurons with larger gene mutations, but the death rate for each set of cells remained constant over time.

The researchers also examined the level of mutant huntingtin protein spread throughout the neurons, outside of inclusion bodies. They found that neurons with larger amounts of mutant huntingtin spread throughout the cell died more rapidly than cells with less of this protein. The amount of mutated protein decreased in other parts of the cell when inclusion bodies formed. Taken together, these findings suggest that inclusion bodies lock up mutant huntingtin and keep it from interfering with the rest of the neuron in ways that can trigger cell death.

These findings provide evidence that inclusion bodies in HD, and possibly other neurodegenerative diseases, help neurons cope with toxic proteins and avoid neurodegeneration. Many researchers have been working to develop ways of interfering with inclusion body formation as potential treatments for HD and other disorders. This study suggests that finding ways to remove mutant proteins diffused throughout the cell might be a more effective approach.

"This approach provides a way to connect cellular changes to fate," says Dr. Finkbeiner. The automated microscope system could be applied to sort out many important questions about how cellular changes or abnormalities affect disease, he adds. He and his colleagues are now planning studies to examine the role of proteasomes – enzyme-filled compartments that break down and recycle proteins – in HD.

Natalie Frazin | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

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

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>