Advances in Dystrophin-based Treatment of Duchenne Muscular Dystro-phy
Duchenne muscular dystrophy(DMD)is a severe progressive hereditary muscle disease,inherited by X-linked negative inheritance,with a male predominance and onset in childhood,and with adverse outcomes including cardiomyopathy and even death,which is a serious threat to the physical and mental health of the global pediatric population.The disease is caused by mutations in the dystrophin gene(dystrophin,DMD),which encodes an abnormal dystrophin protein.The dystrophin protein is located on the inner side of the myocyte membrane,and has four main structural domains:The actin-binding amino-terminal structural domain(ABDI),the central rod structural domain,the cysteine-rich structural domain,and the carboxylate terminal structural domain.The functional side is responsible for maintaining the strength,flexibility and stability of muscle fibers and influencing focal adhesion ten-sion,as well as acting as molecular shock absorbers,protecting cardiac myocytes from plasma membrane damage.More other roles are usually considered in the light of the complexes of which they are a part,including transmitting signals inside and outside of differen-tiated muscle cells and controlling the division kinetics of activated skeletal muscle stem(satellite)cells,etc.It is closely related to the regulation of various parts of the body.The disease is a rare condition and is characterized by laboratory tests,electromyography,MRI genetic testing,muscle biopsy,etc,early diagnosis is very essential for timely intervention treatment and strict care.However,there is currently no cure,and the main therapy is to restore the dystrophin protein to restore normal muscle function,including:The use of read-through therapies,exon jumping therapies,viral vector-mediated gene therapies,and CRISPR/Cas9 gene editing thera-pies,etc;and there are also some methods through regulating the dystrophin protein's analogous protein—utrophin,to achieve the substitution effect.In this article,the authors reviewed the diagnosis of Duchenne muscular dystrophy,the structure,function and muscle relationship of dystrophin proteins,as well as the therapeutic advances through the review of relevant literature at home and abroad.
NETL
NSTL
万方数据
