cellularandmolecularmechanismofmuscieatrophy.pptVIP

Cellular and molecular mechanisms of muscle atrophy * Paolo Bonaldo and Marco Sandri Disease Models Mechanisms 6, 25-39 (2013)doi:10.1242/dmm.010389 1,The ubiquitin-proteasome system. 2,The autophagy-lysosome system. 3,Signaling pathways regulating muscle atrophy: 4,Therapeutic perspectives for counteracting muscle atrophy. Fig. 1. Ubiquitin-proteasome systems in muscle homeostasis. The ubiquitin-proteasome system. several other E3s :Trim32,TRAF6,CHIP,ASB2β. E3s:ubiquitin-protein ligases. KO:konck out. The autophagy-lysosome system. （ROS：活性氧族） Autophagy has a dual role in muscle homeostasis: Too much autophagy impairs myofiber homeostasis, causing excessive removal of cellular components that are needed for normal activities and leading to muscle atrophy when excessive catabolic activity is sustained for long periods. Insufficient autophagy also impairs myofiber homeostasis, leading to accumulation of damaged or dysfunctional cell components, with structural and functional impairment causing muscle weakness. unbalanced autophagy might contribute to sarcopenia. HDAC1 and HDAC2 were found to regulate muscle autophagy by inducing the expression of autophagy genes.(HDACs:组蛋白去乙酰化酶) Myogenin activates the expression of the E3 ubiquitin ligases atrogin-1 and MuRF1. IGF1-Akt-FoxO signaling Inflammatory cytokines and NFκB signaling Myostatin and crosstalk with Akt Glucocorticoid-induced muscle atrophy and the control of protein homeostasis Signaling pathways regulating muscle atrophy: AMPK、nNOS PGC1ɑ、JunB FoxO ＋ － follistatin:卵泡抑素 Glucocorticoid-induced muscle atrophy and the control of protein homeostasis： Therapeutic perspectives for counteracting muscle atrophy. IGF1-AKT axis：Intersection of several different pathways； controls both protein synthesis and protein degradation. Myostatin：Inhibition of myostatin by using soluble ActRIIB prevents and fully reverses skeletal muscle loss