【摘 要】
：
Autophagy dysfunction is a common feature in neurodegenerative disorders caused by toxic,aggregate-prone proteins accumulation.Increasing evidence have demo
【机 构】
：
SchoolofChineseMedicineandMr.&Mrs.KoChi-MingCentreforParkinson'sDiseaseResearch,HongKongBaptistUniv
【出 处】
：
The 7th International Symposium on Autophagy 2015(第七届自噬国际研讨会
论文部分内容阅读
Autophagy dysfunction is a common feature in neurodegenerative disorders caused by toxic,aggregate-prone proteins accumulation.Increasing evidence have demonstrated that genetic or pharmacological activation of transcription factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis, ameliorates neurotoxicity and rescue neurodegenerative phenotypes in several animal models of neurodegenerative diseases.Current known TFEB activators are mainly inhibitors of mammalian target of rapamycin (MTOR).By screening a series of curcumin derivatives, a potent TFEB activator is identified in this study.The small molecule directly binds to TFEB to inhibit MTOR-TFEB-YVVHA interaction, thus promoting TFEB nuclear translocation without inhibiting MTOR activity.By activating TFEB, the compound enhances autophagy and lysosome biogenesis to degrade SNCA/alpha-synuclein in vitro and in vivo.This novel TFEB activator deserves further studies in animal models of neurodegenerative diseases.
其他文献
Autophagy is a dynamic process accomplished by the generation and maturation of autophagosomes.Isolation of autophagosomes and subsequent compositional anal
Autophagy is a conserved event as the bulky catabolic process that responds to nutrient homeostasis and extracellular stress signals in all eukaryotes.When
Background: Our previous finding showed that brain ischemic preconditioning mediates neuroprotection through endoplasmic reticulum (ER) stress-induced autop
Beclin1 is the first identified mammalian autophagy-related protein and serves as a scaffold protein in the Class Ⅲ Phosphatidylinositol 3-Kinase VPS34 com
Autophagy, referred to as macroautophagy, is intracellular degradation pathway that autophagosomic-lysosomal degradation of bulk cytoplasmic product and mis
(Macro-)Autophagy describes a process responsible for the degradation of intracellular proteins and organelles.In recent years, the ULK1/2 complex comprisin
Tumor hypoxia underlies treatment failure and yields more aggressive and metastatic cancer phenotypes.Although therapeutically targeting these hypoxic envir
At the upstream of yeast TORC1, a central regulatory factor of autophagy, there exists a hetero-dimeric G protein Gtr1/Gtr2 complex, which are homologues of
Parkinsons disease (PD), the second most common neurodegenerative disorder, is characterized by the accumulation of pathological protein aggregates (namely
Autophagy is a process of self-cannibalization at the cellular level which involves sequestration of cytosolic components within a double membranous structu