Articles by Wen-An Wang in JoVE
En förbättrad metod för insamling av ryggmärgsvätska från sövda möss Nastasia K-H Lim1,2, Visse Moestrup3,4, Xiao Zhang1, Wen-An Wang5, Arne Møller3,4,6, Fu-De Huang1,4 1Shanghai Advanced Research Institute, University of Chinese Academy of Sciences, Chinese Academy of Science, 2Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Science, 3Center of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, 4Sino-Danish Center for Education and Research (SDC), 5Department of Neurology, Xinhua Hospital Chongming Branch Affiliated to Shanghai Jiao Tong University School of Medicine, 6Department of Nuclear Medicine and PET-centre, Aarhus University Hospital Det här protokollet beskriver en förbättrad teknik för riklig insamling av cerebrospinalvätska (CSF) med ingen förorening från blodet. Med större provsamling och renhet, kan fler analyser utföras med CSF för att vidareutveckla vår förståelse av sjukdomar som påverkar hjärnan och ryggmärgen.
Other articles by Wen-An Wang on PubMed
Downregulation of RBO-PI4KIIIα Facilitates Aβ42 Secretion and Ameliorates Neural Deficits in Aβ42-Expressing Drosophila The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. May, 2017 | Pubmed ID: 28424219 Phosphoinositides and their metabolizing enzymes are involved in Aβ42 metabolism and Alzheimer's disease pathogenesis. In yeast and mammals, Eighty-five requiring 3 (EFR3), whose Drosophila homolog is Rolling Blackout (RBO), forms a plasma membrane-localized protein complex with phosphatidylinositol-4-kinase Type IIIα (PI4KIIIα) and a scaffold protein to tightly control the level of plasmalemmal phosphatidylinositol-4-phosphate (PI4P). Here, we report that RBO binds to Drosophila PI4KIIIα, and that in an Aβ42-expressing Drosophila model, separate genetic reduction of PI4KIIIα and RBO, or pharmacological inhibition of PI4KIIIα ameliorated synaptic transmission deficit, climbing ability decline, premature death, and reduced neuronal accumulation of Aβ42 Moreover, we found that RBO-PI4KIIIa downregulation increased neuronal Aβ42 release and that PI4P facilitated the assembly or oligomerization of Aβ42 in/on liposomes. These results indicate that RBO-PI4KIIIa downregulation facilitates neuronal Aβ42 release and consequently reduces neuronal Aβ42 accumulation likely via decreasing Aβ42 assembly in/on plasma membrane. This study suggests the RBO-PI4KIIIα complex as a potential therapeutic target and PI4KIIIα inhibitors as drug candidates for Alzheimer's disease treatment.SIGNIFICANCE STATEMENT Phosphoinositides and their metabolizing enzymes are involved in Aβ42 metabolism and Alzheimer's disease pathogenesis. Here, in an Aβ42-expressing Drosophila model, we discovered and studied the beneficial role of downregulating RBO or its interacting protein PI4KIIIα-a protein that tightly controls the plasmalemmal level of PI4P-against the defects caused by Aβ42 expression. Mechanistically, RBO-PI4KIIIα downregulation reduced neuronal Aβ42 accumulation, and interestingly increased neuronal Aβ42 release. This study suggests the RBO-PI4KIIIα complex as a novel therapeutic target, and PI4KIIIα inhibitors as new drug candidates.