Navigation Links
New clues about the basis of muscle wasting disease

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.

Professor Laura Machesky and colleagues from the CRUK Beatson Institute for Cancer Research in Glasgow, tested cultures of muscle cells that displayed mutations of the ACTA1 gene to determine how the mutations affected the biochemical pathways leading to the muscle damage seen in nemaline myopathy.

The ACTA1 gene controls the production of actin, one of the main structural proteins in muscle; mutations in this gene cause 15-20% of cases of nemaline myopathy, an inherited muscle wasting disease similar to muscular dystrophy. Around 140 different mutations of the ACTA1 gene can occur; around a third of these have been biochemically characterized to determine how they affect actin. The mutations cause a wide variety of defects in the biochemical behaviour of actin, but all cause defects in the structure of muscle cells leading to cell and tissue damage and wasting. The researchers discovered that not only do disease-causing mutations in actin lead to weakening of the cell's internal support system, but they also cause changes in the genetic control of other biochemical pathways such as the serum-response factor pathway (SRF). When actin binds to a protein called MAL (originally named megakaryoblastic leukaemia-1) in the cell's nucleus, it switches on the SRF pathway. Actin damaged by mutations doesn't bind properly and the SRF pathway isn't fully activated.

The SRF signalling pathway has a role in muscle development and maintenance. The presence of myopathy-causing mutant actin protein leads to alteration in the pathway that could promote muscle cell degeneration and death or interfere with normal growth and repair. The majority of ACTA1 mutants examined in this study altered the serum response factor signalling pathway, indicating that changes in this pathway may be a major factor in actin-based nemaline myopathy and that this area could be used to develop therapies for patients.

Nemaline myopathies are sometimes called rod body myopathies as the damaged proteins form abnormal thread-like rods, called nemaline bodies, in the muscle cells. There are a number of different types of rod myopathies and they affect both males and females. In the majority of cases (90%) the condition becomes apparent at birth or early childhood, although in very rare cases, it does not become apparent until adulthood. Rod myopathies are estimated to affect 1 in 50,000 individuals.

Commenting on the findings, Professor Machesky said, "More research now needs to be done to determine whether cells in patients have the same changes that we saw in cells in the laboratory. We used the drugs Jasplakinolide and Cytochalasin D, which target the actin-MAL complex, to reverse the effects of the mutant actin - but these drugs are toxic at high levels as they also disrupt the actin filaments and thus the cell's structure. If they could be modified or used at low concentrations they may prove useful leads to drug development."

Marita Pohlschmidt director of research at the Muscular Dystrophy Campaign said, "Nemaline myopathy is a very rare condition that can be difficult to diagnose, because it is caused by a defect in one of several genes. The research presented in this paper is an important contribution to understanding what causes the muscle wasting in about a fifth of all people affected with this devastating condition. The results will be vital for the future development of treatments for those affected by nemaline myopathy."


Contact: Dianne Stilwell
Biochemical Journal

Related biology news :

1. Study begins to reveal clues to the cause and progression of sepsis
2. Chlamy genome holds clues for renewable energy, the environment and human health
3. How schizophrenia develops: Major clues discovered
4. Tiny fish can yield big clues to Delaware River health
5. Fossils excavated from Bahamian blue hole may give clues of early life
6. Study uncovers clues to cystic fibrosis gene dysfunction and gastrointestinal disease
7. Cornell researcher seeks clues to how tuberculosis infects cells
8. Cognitive, genetic clues identified in imaging study of alcohol addiction
9. HIV isolate from Kenya provides clues for vaccine design
10. Mummy lice found in Peru may give new clues about human migration
11. Tomato pathogen genome may offer clues about bacterial evolution at dawn of agriculture
Post Your Comments:
(Date:11/10/2015)... 10, 2015  In this report, the ... of product, type, application, disease indication, and ... report are consumables, services, software. The type ... biomarkers, efficacy biomarkers, and validation biomarkers. The ... diagnostics development, drug discovery and development, personalized ...
(Date:11/2/2015)... , Nov. 2, 2015  SRI International has been ... provide preclinical development services to the National Cancer Institute ... will provide scientific expertise, modern testing and support facilities, ... preclinical pharmacology and toxicology studies to evaluate potential cancer ... The PREVENT Cancer Drug Development Program is an ...
(Date:10/29/2015)... BOSTON , Oct. 29, 2015  Connected health ... phenomena driving the explosion of technology-enabled health and wellness, ... his new book, The Internet of Healthy ... apps, sensors or smartphones even existed, Dr. Kvedar, vice ... model of health care delivery, moving care from the ...
Breaking Biology News(10 mins):
(Date:12/1/2015)... ... December 01, 2015 , ... RURO, Inc., ... selling system laboratory animal colony management software solution, ezColony®, is now available as ... IT resources., , Many organizations are moving to cloud-hosting ...
(Date:12/1/2015)... Dallas, Texas (PRWEB) , ... December 01, 2015 ... ... its annual global meeting this month and Dr. J. Kyle Mathews ... worldwide.” This includes the new single site hysterectomy. , An experienced urogynecologist, founder ...
(Date:11/30/2015)... ... November 30, 2015 , ... Global Stem Cells ... 10000 in the Santiago Marriott. The Global Stem Cells Group GMP facility is ... team of qualified medical researchers and practitioners, experienced in administering stem cell protocols ...
(Date:11/30/2015)... , Nov. 30, 2015  Culprits beware, ... assistant chemistry professor Jan Halámek, is taking crime ...   --> ...   --> --> ... UAlbany have discovered a straightforward concept for identifying ...
Breaking Biology Technology: