Impaired protein degradation causes muscle diseases

by Julia Weiler

New insights into certain muscle diseases, the filaminopathies, are reported by an international research team led by Dr. Rudolf Andre Kley of the RUB's University Hospital Bergmannsheil in the journal Brain. The scientists from the Neuromuscular Centre Ruhrgebiet (headed by Prof. Matthias Vorgerd) at the Neurological University Clinic (Director: Prof. Martin Tegenthoff) cooperated with colleagues from eleven institutes in seven countries. Among other things they found that protection mechanisms to combat abnormal protein deposits do not work properly in filaminopathy patients. This opens up new starting points for therapies that the team aims to test on cell cultures.

How filaminopathies develop

Mutations in the filamin C gene (FLNC) cause filaminopathies, which are manifested through to the point of loss of the ability to walk. are composed of myofibrils, for the development and maintenance of which the protein filamin C is crucial. The mutations examined in the study bring about a so-called myofibrillar myopathy: the myofibrils disintegrate in certain places and mutant filamin C and other proteins aggregate massively in the muscle fibres.

Support of protein degradation does not start on time

The researchers showed that the diseased protein deposits interfere with the usually occurring in cells. Normally, cells produce what are known as , which promote the degradation of protein deposits and make sure that other proteins assume their correct three-dimensional structure. "However, these protection mechanisms only seem to be increasingly activated when the critical point is exceeded. It looks as if the 'fire brigade' was called too late", says Dr. Kley. "We hope to positively influence the course of the disease by means of early treatment with substances that stimulate the production of heat shock proteins or affect the protein degradation in other ways. To study this, we have developed a cell culture model that allows us to carry out the first therapy studies in the laboratory."

Clinical picture more precisely characterised

The study of filaminopathy patients also enables the researchers to describe the disease more accurately now. The heart is more affected by the disease than previously thought, which may cause sudden cardiac death. It was also confirmed that pathological remodelling processes in the leg muscles conform to a specific pattern, which is visible on magnetic resonance imaging pictures. "This enables us to distinguish filaminopathies from other muscle diseases within the group of myofibrillar myopathies", explains Dr. Kley.

More information: R.A. Kley et al. (2012): Pathophysiology of protein aggregation and extended phenotyping in filaminopathy, Brain, doi: 10.1093/brain/aws200

add to favorites email to friend print save as pdf

Related Stories

New clues about the basis of muscle wasting disease

Mar 12, 2010

New findings that shed light on how genetic damage to muscle cell proteins can lead to the development of the rare muscle-wasting disease, nemaline myopathy, are reported today (15 March) in the Biochemical Journal.

Recommended for you

Gamers helping in Ebola research

6 hours ago

Months before the recent Ebola outbreak erupted in Western Africa, killing more than a thousand people, scientists at the University of Washington's Institute for Protein Design were looking for a way to stop the deadly virus.

Carcinogenic role of a protein in liver decoded

9 hours ago

The human protein EGFR controls cell growth. It has mutated in case of many cancer cells or exists in excessive numbers. For this reason it serves as a point of attack for target-oriented therapies. A study ...

A new way to diagnose malaria, using magnetic fields

Aug 31, 2014

Over the past several decades, malaria diagnosis has changed very little. After taking a blood sample from a patient, a technician smears the blood across a glass slide, stains it with a special dye, and ...

User comments