Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Penn researchers find potential in yeast for selecting Lou Gehrig's disease drugs

22.04.2008
Researchers from the University of Pennsylvania School of Medicine are developing a novel approach to screen for drugs to combat neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, using yeast cells. In recent months a number of mutations have been found in a disease protein called TDP-43, which is implicated in ALS and certain types of frontotemporal dementia (FTD).

“We've created a yeast model, the same cells that bakers and brewers use to make bread and beer, to express TDP-43,” explains lead author Aaron D. Gitler, PhD, Assistant Professor of Cell and Developmental Biology. “Remarkably, this protein formed clumps in our simple yeast cells just like it does in human nerve cells. In our paper we determine which segments of the mutated TDP-43 protein cause it to aggregate and which parts cause it to be toxic.” Gitler and colleagues report their findings in this week’s advance online issue of the Proceedings of the National Academy of Sciences.

Two years ago, other Penn investigators found that TDP-43 accumulated abnormally in post-mortem brain or nervous system tissue from individuals diagnosed with either ALS or FTD. TDP-43 is normally involved in RNA and DNA processing, among other cellular tasks. The recent TDP-43 mutation studies confirm the protein’s role in causing disease.

The clumping process of proteins takes decades in humans but the researchers could model the process within a matter of hours in yeast cells. This now allows for rapid genetic screening to identify proteins that can reverse the harmful effects of the disease protein; visualizing the clumping; and testing molecules that could eliminate or prevent clumping.

... more about:
»Disease »FTD »Gitler »Mutation »Screen »TDP-43 »clumps »toxic »yeast

“Our yeast model will be a powerful tool for performing large-scale drug screens to look for small molecules that can prevent TDP-43 from aggregating or that can protect cells from aggregated TDP-43,” notes Gitler.

Normally, TDP-43 stays in the nucleus, but in ALS and FTD it somehow gets sequestered into the cell’s cytoplasm, where it forms clumps. “When we put TDP-43 in yeast cells at normal human levels, it remained in the nucleus,” explains Gitler. “However, when it was expressed at higher levels, thereby overwhelming the quality control systems of the cell, TDP-43 clumped in the cytoplasm. At even higher levels, TDP-43 became toxic to the yeast cells, making them unable to grow.” This experiment suggests, for the first time, that TDP-43 clumps can be a direct cause of cell toxicity.

In earlier studies at Penn, researchers found fragments of TDP-43 that were abundant in the clumps found in the post-mortem tissue of ALS and FTD patients. Knowing this, Gitler and colleagues chopped TDP-43 into many fragments to find the segments that are responsible for clumping and toxicity. They found a very similar segment that was also toxic to yeast cells. Designs of future drugs will depend on what part of the TDP-43 protein needs to be disabled.

The researchers are able to overexpress every yeast gene to determine which genes can rescue the yeast cells from the TDP-43 toxicity. In addition to these genetic screens, Gitler and colleagues are pursuing drug screens with their TDP-43 model. “We can screen hundreds of thousands of small molecules to see which can get into a yeast cell and prevent TDP-43 from being toxic,” says Gitler. “Then we can take the hits we find and test them in animal models. We have already made mutations identical to what have been found in patients and have introduced those in the yeast model.”

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

Further reports about: Disease FTD Gitler Mutation Screen TDP-43 clumps toxic yeast

More articles from Life Sciences:

nachricht Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo

nachricht Research reveals how order first appears in liquid crystals
23.05.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
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

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Research reveals how order first appears in liquid crystals

23.05.2018 | Life Sciences

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

NIST puts the optical microscope under the microscope to achieve atomic accuracy

23.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>