The autophagy-lysosome pathway:a potential target in the chemical and gene therapeutic strategies for Parkinson’s disease

Parkinson’s disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such asα-synuclein in neurons.As one of the major intracellular degradation pathways,the autophagy-lysosome pathway plays an important role in eliminating these proteins.Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance ofα-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson’s disease.Moreover,multiple genes associated with the pathogenesis of Parkinson’s disease are intimately linked to alterations in the autophagy-lysosome pathway.Thus,this pathway appears to be a promising therapeutic target for treatment of Parkinson’s disease.In this review,we briefly introduce the machinery of autophagy.Then,we provide a description of the effects of Parkinson’s disease–related genes on the autophagy-lysosome pathway.Finally,we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy–lysosome pathway and their applications in Parkinson’s disease.

Chemical ablation of the gallbladder using alcohol in cholecystitis after palliative biliary stenting

Chemical ablation of the gallbladder is effective in patients at high risk of complications after surgery. Percutaneous gallbladder drainage is an effective treatment for cholecystitis; however, when the drain tube cannot be removed because of recurrent symptoms, retaining it can cause problems. An 82-year-old woman presented with cholecystitis and cholangitis caused by biliary stent occlusion and suspected tumor invasion of the cystic duct. We present successful chemical ablation of the gallbladder using pure alcohol, through a percutaneous gallbladder drainage tube, in a patient who developed intractable cholecystitis with obstruction of the cystic duct after receiving a biliary stent. Our results suggest that chemical ablation therapy is an effective alternative to surgical therapy for intractable cholecystitis.

Design and therapeutic application of sodium alginate-based hydrogel with biodegradability and catalytic activity

How to efficiently treat cancer in a minimally invasive manner has become one of the major focuses of recent developments in biomedicine.In this research,biodegradable sodium alginate(SA)hydrogel encapsulated with NaHCO_(3)and glucose oxidase(GOX)was synthesized using Fe^(3+)as the crosslinker for the tumor chemodynamic therapy(CDT)and starvation therapy(ST).Material safety assessments revealed that this hydrogel possesses good in vitro and in vivo security.In tumor microenvrionment(TME),the Fe^(3+)further reacted with the intracellular glutathione and was transformed into Fe^(2+),which triggered the Fenton reaction with the H_(2)O_(2)within TME and produced abundant highly toxic·OH(hydroxyl radicals)for efficient tumor CDT.Furthermore,the GOXcatalyzed the enzymolysis of glucose to consume the nutrient of the tumor and enhance the H_(2)O_(2)level in TME.Besides,the CO_(2)bubbles that were generated from the decomposing of NaHCO_(3)promoted the contact between glucose and GOX.Findings in this research would have important implications for the present status of tumor therapy.