Biology Reference
In-Depth Information
2004
), prior to the age when denervation becomes prevalent, suggesting that
denervation is only a single component of the overall sarcopenia response.
Additional factors that are likely to contribute to sarcopenia include aging-
associated reductions in endogenous GH and anabolic steroids; the activa-
tion of
B and TNF-alpha; and
increased apoptosis (
Sakuma and Yamaguchi, 2012
). Additionally, increased
activity of the ubiquitin-proteasome system, which controls degradation of
protein, may be a causative factor in sarcopenia (
Altun et al., 2010
). Skeletal
muscle mass also diminishes in certain diseases including cancer and HIV, a
process termed cachexia (
Shum and Polly, 2012
); the similarities between
sarcopenia and cachexia are numerous, suggesting that they may be regu-
lated by similar molecular pathways (
Lenk et al., 2010
).
inflammation pathways, such as NF-
k
2.6. Muscular dystrophies
Mutations in several genes lead to progressive weakening and degeneration
of the skeletal muscle. The most common form is Duchenne's muscular dys-
trophy (DMD), which occurs with an incidence of 1 in 3600 males (
Ouyang
et al., 2008
). The average life expectancy for patients with DMD is approx-
imately 25 years, and there is no known cure. DMD is due to mutation of
the dystrophin gene, with loss of expression of dystrophin (
Hoffman and
Kunkel, 1989; Le Rumeur et al., 2010
). A related, but less severe form, ter-
med Becker's muscular dystrophy is due to mutations which result in trun-
cation or misfolding of dystrophin (
Acsadi et al., 2012
). Loss or mutation of
dystrophin causes instability in sarcolemma-extracellular matrix interaction,
such that contractile function damages the fibers, leading to loss of the fibers
due to necrosis and other processes. There are canine (Golden Retriever
muscular dystrophy;
Miyazato et al., 2011
) and murine (mdx mice)
(
Grounds et al., 2008
) animal models that somewhat recapitulate the key fea-
tures of the human disease. Therapeutic strategies currently being consid-
ered for DMD/Becker muscular dystrophy include pharmacological
agents, which may reduce symptoms (
D'Angelo et al., 2012
), as well as gene
therapy (
Odom et al., 2010; Tedesco et al., 2011
) and regenerative
medicine-based approaches (
Kazuki et al., 2010
).
Muscular dystrophies also arise from mutations affecting proteins other
than dystrophin. Congenital muscular dystrophies (CMD, considered con-
genital as the symptoms appear in infants), correspond to mutations in a vari-
ety of structural, nuclear, and endoplasmic reticulum proteins (
Bertini et al.,
2011; Clement et al., 2012
). In a recent study, the majority of the CMD
Search WWH ::
Custom Search