Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0024591 (
malignant hyperthermia
)
2,353
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Central core disease (CCD) is a congenital myopathy linked to mutations in the ryanodine receptor type 1 (RYR1), the sarcoplasmic reticulum Ca
2+
release channel of skeletal muscle. CCD is characterized by formation of amorphous
cores
within muscle fibers, lacking mitochondrial activity. In skeletal muscle of RYR1
Y522S/WT
knock-in mice, carrying a human mutation in RYR1 linked to
malignant hyperthermia
(MH) with
cores
, oxidative stress is elevated and fibers present severe mitochondrial damage and
cores
. We treated RYR1
Y522S/WT
mice with N-acetylcysteine (NAC), an antioxidant provided
ad libitum
in drinking water for either 2 or 6 months. Our results show that 2 months of NAC treatment starting at 2 months of age, when mitochondrial and fiber damage was still minimal, (i) reduce formation of
unstructured
and
contracture cores
, (ii) improve muscle function, and (iii) decrease mitochondrial damage. The beneficial effect of NAC treatment is also evident following 6 months of treatment starting at 4 months of age, when structural damage was at an advanced stage. NAC exerts its protective effect likely by lowering oxidative stress, as supported by the reduction of 3-NT and
SOD2
levels. This work suggests that NAC administration is beneficial to prevent mitochondrial damage and formation of
cores
and improve muscle function in RYR1
Y522S/WT
mice.
...
PMID:Antioxidant Treatment Reduces Formation of Structural Cores and Improves Muscle Function in RYR1
Y522S/WT
Mice. 2906 63
