@entity3986 in XXXX by SERCA overexpression in skeletal muscle.

@entity82 @entity39 @entity19 @entity908 @entity3986 @entity73352 @entity14571 @entity601 @entity73353 @entity141 @entity2057 @entity121
@entity3986 ( @entity3986 ) comprise a group of @entity121 characterized by progressive @entity2057 and often premature death. The primary defect common to most @entity3986 involves disruption of the dystrophin-glycoprotein complex (DGC). This leads to sarcolemmal instability and @entity141 influx, inducing cellular @entity39 . Here we have shown that the @entity3986 phenotype observed in   -sarcoglycan   null ( @entity73352 (   /   )) @entity19 and dystrophin mutant mdx @entity19 is dramatically improved by skeletal muscle   specific overexpression of sarcoplasmic reticulum @entity141 ATPase 1 ( @entity73353 ). Rates of myofiber central nucleation, tissue @entity82 , and serum @entity908 kinase levels were dramatically reduced in @entity73352 (   /   ) and mdx @entity19 with the @entity73353 transgene, which also rescued the loss of exercise capacity in @entity73352 (   /   ) @entity19 . Adeno-associated virus   @entity14571 (AAV- @entity14571 ) gene therapy in the gastrocnemius muscle of @entity73352 (   /   ) @entity19 mitigated @entity3986 . @entity73353 overexpression reversed a defect in sarcoplasmic reticulum @entity141 reuptake that characterizes @entity3986 and reduced total cytosolic @entity141 . Further, @entity73353 overexpression almost completely rescued the @entity3986 phenotype in a @entity19 model of @entity601 driven solely by @entity141 influx. Mitochondria isolated from the muscle of @entity73353 - @entity73352 (   /   ) @entity19 were no longer swollen and calpain activation was reduced, suggesting protection from @entity141 -driven @entity39 . Our results suggest a novel therapeutic approach using @entity73353 to abrogate the altered intracellular @entity141 levels that underlie most forms of @entity601 .
