Featured Research

from universities, journals, and other organizations

New clues about the basis of muscle wasting disease

Date:
March 14, 2010
Source:
Biochemical Journal
Summary:
New findings shed light on how genetic damage to muscle cell proteins can lead to the development of the rare muscle-wasting disease, nemaline myopathy.

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 March 15 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."


Story Source:

The above story is based on materials provided by Biochemical Journal. Note: Materials may be edited for content and length.


Journal Reference:

  1. Visegrady et al. Myopathy-causing Actin Mutations Promote Defects in Serum Response Factor Signaling. Biochemical Journal, 2010; DOI: 10.1042/BJ20091641

Cite This Page:

Biochemical Journal. "New clues about the basis of muscle wasting disease." ScienceDaily. ScienceDaily, 14 March 2010. <www.sciencedaily.com/releases/2010/03/100312133731.htm>.
Biochemical Journal. (2010, March 14). New clues about the basis of muscle wasting disease. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2010/03/100312133731.htm
Biochemical Journal. "New clues about the basis of muscle wasting disease." ScienceDaily. www.sciencedaily.com/releases/2010/03/100312133731.htm (accessed July 30, 2014).

Share This




More Health & Medicine News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Generics Eat Into Pfizer's Sales

Generics Eat Into Pfizer's Sales

Reuters - Business Video Online (July 29, 2014) Pfizer, the world's largest drug maker, cut full-year revenue forecasts because generics could cut into sales of its anti-arthritis drug, Celebrex. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile: iPhone Android Web
      Follow: Facebook Twitter Google+
      Subscribe: RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins