Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Blazing a new path for Emery-Dreifuss Muscular Dystrophy

13.12.2005


News from the Cell Biology Meeting in San Francisco



Bushwhacking through the cellular jungle, researchers are always relieved to stumble across a known molecular pathway. Imagine their excitement at finding a major intersection in unmapped territory. Antoine Muchir and Howard Worman at the Columbia University College of Physicians & Surgeons in New York and their colleagues in France, have discovered a cellular "crossroads" that links the function of the MAP kinase pathway, long implicated in heart failure, to A-type nuclear lamins. Mutations in LMNA, the gene encoding all A-type lamins, cause at least two heritable diseases that affect the heart: Dilated Cardiomyopathy with conduction system defects (DC) and Emery-Dreifuss Muscular Dystrophy (EDMD), which affects muscles and tendons in addition to causing life-threatening cardiomyopathy and cardiac conduction system defects. Muchir presented the findings Sunday at the 45th Annual Meeting of the American Society for Cell Biology in San Francisco.

Instead of using a machete, these cellular trailblazers followed a mouse. The researchers created a "knock-in" model mouse by replacing the normal mouse LMNA gene with a mutated human gene that causes EDMD. Lamin proteins form a network of filaments inside the nucleus, conferring shape and mechanical stability, but they are also "used" by many other proteins and pathways in the nucleus, for a variety of purposes. Mutations in LMNA cause a wide range of human diseases--besides DC and EDMD, these "laminopathies" include other heritable forms of muscular dystrophy, lipodystrophy, neuropathy, bone disorders and accelerated aging (progeria) syndromes.


But no one knew why defective A-type lamins, which are expressed in almost all differentiated cells in the body, specifically affected the heart. Muchir and collaborators used their ’knock-in’ EDMD model mouse to test the immediate effects of this lamin mutation on gene expression. Taking cardiac muscle from the genetically altered mice, the researchers used "gene chip" DNA microarrays to rapidly screen for changes in expression levels. Unlike normal mouse hearts, the mutant hearts showed increased expression of genes encoding MAP kinases, which were previously implicated in heart hypertrophy and failure. These same experiments also revealed changes in the expression of genes encoding other components of the muscle contraction apparatus, an angiogenesis factor and a heart hormone. All three play roles in other forms of cardiomyopathy.

As for MAP kinases, the laminopathy connection couldn’t have turned up a more promising pathway. Short for "mitogen-activated pathway," the MAP kinase family influences many aspects of cell life including gene expression, mitosis, differentiation and apoptosis (programmed cell death). MAP kinases have attracted basic researchers for decades, and pharmaceutical companies have begun developing MAP kinase inhibitors as potential therapeutic agents. The trail blazed here by Muchir and colleagues opens the possibility that MAP kinase inhibitors could be used to treat lamin-related cardiomyopathies.

John Fleischman | EurekAlert!
Further information:
http://www.ascb.org

More articles from Life Sciences:

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
21.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
21.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

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

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>