ABSTRACT
Wilson disease (WD) is a treatable neurological inherited disorder characterized by copper metabolism impairment. Metal chelating drugs, such as penicillamine, have been used to treat WD for decades, is exposuring its limitations of effect and utilize sphere. Genetic therapy was considered as the most potential way of curing WD, is still can only be achieved in the laboratory, which have massive problems to solve before its clinical utilization. Based on this, we started to research the curative mechanism of traditional Chinese medicine(TCM) donated by national natural science fund project funding, found that TCM formula Gandou decoction regulate the metabolic disorders caused by liver cells and neurons apoptosis, autophagy, such as programmed cell death,from the molecular pathways of copper metabolism, Wnt/β-catenin pathway and mitogen-activated protein kmase(MAPK) pathways regulating liver damage such as cell signaling pathways, extracellular signal-regulated kinase(ERK) pathway and liver kinase B1(LKB1)/adenosine monophosphate activated protein kinase(AMPK) pathway and the cell signaling pathway of neuronal damage. The above experimental results were verified by TX mice, a reliable WD animal models. This paper aimed to systematically review the research of GDD therapeutic mechanisms from the sight of programmed cell death, including aptosis and autophagy, and provided theoretical for formula optimization. In addition, we elaborated some assumptions and feasible advice for the further research of GDD therapeutic mechanism.
ABSTRACT
Since its discovery in the 1970s,the mitochondrial permeability transition(mPT)has been proposed to be a strate?gic regulator of programmed cell death(PCD). The mPT denotes an increase in the mitochondrial inner membrane permeability to sol?utes with molecular masses up to about 1.5×103. It is presumed to be mediated by an opening of a channel,the mPT pore(mPTP), whose molecular nature remains a mystery. Intense research efforts have focused on elucidating the molecular components of the mPTP because it may help to better understand and treat various pathologies ranging from neurodegenerative and cardiac diseases to cancer. This article briefly reviews the new progress of mPTP structural models and its specific molecular mechanisms of regulating PCD , then demonstrates the feasibility of using the mPTP-targeting agents as a potential alternative strategy for effective management of PCD.
ABSTRACT
Since its discovery in the 1970s, the mitochondrial permeability transition(mPT)has been proposed to be a strategic regulator of programmed cell death(PCD). The mPT denotes an increase in the mitochondrial inner membrane permeability to solutes with molecular masses up to about 1.5×103. It is presumed to be mediated by an opening of a channel, the mPT pore(mPTP), whose molecular nature remains a mystery. Intense research efforts have focused on elucidating the molecular components of the mPTP because it may help to better understand and treat various pathologies ranging from neurodegenerative and cardiac diseases to cancer. This article briefly reviews the new progress of mPTP structural models and its specific molecular mechanisms of regulating PCD, then demonstrates the feasibility of using the mPTP-targeting agents as a potential alternative strategy for effective management of PCD.
ABSTRACT
Autophagy occurs in all types of eukaryotic cells, which has a rigid connection with the normal or abnormal development of cells and is associated with many diseases. There're lots of molecular control elements and multiple signaling pathways involved in regulating autophagy. As a form of type Ⅱ programmed cell death, autophagy participates in maintaining cell homeostasis and pathogenesis of various of diseases through interacting with apoptotic pathway. Recent studies show that autophagy has effects on the occurrence and development of tumor cells through influencing on cell cycle, apoptosis-associated factors and angiogenesis.