The variability in neurological deficits in Duchenne muscular dystrophy patients may be explained by differences in dystrophin glycoprotein complexes in the brain and muscle

Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic neuromuscular disorder. The variability in neurologic deficits in DMD patients may be explained by the fact that (1) dystrophin containing complexes in the brain are more stable than dystrophin containing complexes in the muscle (2) neurons are not affected by the same stresses as muscle and (3) neurons have a greater capacity to buffer increases in intracellular calcium levels. In the muscle, the loss of dystrophin and subsequent loss of dystrophin-associated proteins (DAPs) affects the stability of the dystrophin-glycoprotein complex and calcium ion channels. It causes the sarcolemma of the muscle to tear and calcium ion leak. The subsequent calcium influx leads to calcium dependant proteolysis. In the brain, the structure of the dystrophin-containing complexes is completely different from the muscle. There are several dystrophin isoforms that combine with a completely different set of proteins compared to the muscle to form several different dystrophin-containing complexes. In addition, the loss of dystrophin does not affect the expression of DAPs. The heterogeneity of dystrophin-containing complexes and the continued expression of DAPs will result in more stable dystrophin-containing complexes in the DMD brain. Muscles are under more stress than neurons as they undergo contractions. This combined with txhe fact that the neurons have a better ability to buffer increases in calcium would suggest that neurons...
Source: NeuroReport - Category: Neurology Tags: Neurodegeneration Source Type: research