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| 1 | Endosome-mediated retrograde axonal transport of P2X3 receptor signals in primary sensory neurons显示文摘Neurotrophins 和他们的受体采用发信号的内涵体播送后退信号。然而,机制后退发信号因为另外的 ligand/receptor 系统糟糕被理解。这里,我们报导 purinergic (P) 2X 3 受体的信号,一条门 ATP 的离子隧道, retrogradely 在背面的根中心(DRG ) 被搬运神经原轴突。我们发现了那 Rab5,小 GTPase,控制早 P2X 3 受体排序进内涵体,当 Rab7 调停时快后退 P2X 3 受体的运输。Intraplantar 注射和 axonal 申请进 α 的 microfluidic 房间;, β -methylene-ATP (α, β -MeATP), P2X 选择收缩筋,提高了 endocytosis 并且后退 P2X 3 受体的运输。α, β激活的 -MeATP-induced Ca 2+ 流入由蛋白质 kinase C 组成的一条小径,病毒的 oncogene 和细胞外的调整信号的蛋白质 kinase (英皇家空军之阶级最低之兵) ,它与 endocytic P2X 3 受体联系了到形成表明内涵体的老鼠肉瘤。类脂化合物椽子的混乱废除了 α, β -MeATP-induced 英皇家空军之阶级最低之兵 phosphorylation, endocytosis 并且后退 P2X 3 受体的运输。而且,有 α 的外部轴突的治疗;, β -MeATP 在 DRG 的房间身体增加了英皇家空军之阶级最低之兵和营地反应元素绑定蛋白质的激活水平神经原和提高的 neuronal 易兴奋性。也的缺陷在 vivo 的基于微导管的 axonal 运输或在 vitro 的 dynein 功能堵住了 α, β -MeATP-induced 后退信号。这些结果显示那 P2X 3 激活受体的信号在主要感觉神经原经由 retrogradely 搬运的内涵体被播送并且为门 ligand 的隧道提供新奇发信号机制。 | Xu-Qiao Chen Bin Wang Chengbiao Wu Jin Pan Bo Yuan Yuan-Yuan Su Xing-Yu Jiang Xu Zhang Lan Bao | 2012 | Cell Research2012，22，4： | 8 |
| 2 | Current advances in using neurotrophic factors to treat neurodegenerative disorders显示文摘Neurotrophic factors are best known for their roles in both development and continued maintenance of the nervous system.Their strong potential to elicit pro-survival and pro-functional responses in neurons of the peripheral and central nervous system make them good drug candidates for treatment of a multitude of neurodegenerative disorders.However,significant obstacles remain and need to be overcome before translating the potential of neurotrophins into the therapeutic arena.This article addresses current efforts and advances in resolving these challenges and provides an overview of roadmaps for future translational research and neurotrophin-based drug developments. | April M Weissmiller Chengbiao Wu | 2012 | Translational Neurodegeneration2012，1，1： | 7 |
| 3 | Uncoupling neurotrophic function from nociception of nerve growth factor: what can be learned from a rare human disease?显示文摘Nerve growth factor(NGF) is a powerful trophic factor that provides essential support for the survival and differentiation of sympathetic and sensory neurons during development. However, NGF also activates nociceptors contributing significantly to inflammatory pain and neuropathic pain after tissue injury. As such anti-NGF based therapies represent a promising strategy for pain management. Because of dose-dependent serious side effects such as back pain, injection site hyperalgesia, clinical trials of using NGF to treat various disorders such as diabetic neuropathies, chemotherapy-induced and human immunodeficiency virus-associated peripheral neuropathies were all discontinued. Thus far, worldwide clinical applications of NGF in treating patients are very limited except in China. Hereditary sensory autonomic neuropathy type V(HSAN V) is an extremely rare disease. Genetic analyses have revealed that HSAN V is associated with autosomal recessive mutations in NGF. One of the mutations occurred at the 100^(th) position of mature NGF resulting in a change of residue from arginine to tryptophan(R100W). Although those HSAN V patients associated with the NGF^(R100W) mutation suffer from severe loss of deep pain, bone fractures and joint destruction, interestingly patients with the NGF^(R100W) mutation do not show apparent cognitive deficits, suggesting important trophic support function is preserved. We believe that NGF^(R100W) provides an ideal tool to uncouple the two important functions of NGF: trophic versus nociceptive. Studies from investigators including ourselves have indeed confirmed in animal testing that the NGF^(R100W) no longer induced pain. More importantly, the trophic function seemed to be largely preserved in NGF harboring the R100W mutation. On the mechanistic level, we found that the NGF^(R100W) mutation was capable of binding to and signaling through the tyrosine receptor kinase A receptor. But its ability to bind to and activate the 75 kDa neurotrophic factor was significantly diminished. The significance of these findings is at least two folds: 1) the NGF^(R100W) mutation can be used as an alternative to the wildtype NGF to treat human conditions without eliciting pain; and 2) the 75 kDa neurotrophic factor may serve as a novel target for pain management. We will discuss all the details in this mini-review. | Kijung Sung Wanlin Yang Chengbiao Wu | 2019 | Neural Regeneration Research2019，14，4： | 5 |
| 4 | Upregulation of RIN3 induces endosomal dysfunction in Alzheimer’s disease显示文摘Background In Alzheimer’s Disease(AD),about one-third of the risk genes identified by GWAS encode proteins that function predominantly in the endocytic pathways.Among them,the Ras and Rab Interactor 3(RIN3)is a guanine nucleotide exchange factor(GEF)for the Rab5 small GTPase family and has been implicated to be a risk factor for both late onset AD(LOAD)and sporadic early onset AD(sEOAD).However,how RIN3 is linked to AD pathogenesis is currently undefined.Methods Quantitative PCR and immunoblotting were used to measure the RIN3 expression level in mouse brain tissues and cultured basal forebrain cholinergic neuron(BFCNs).Immunostaining was used to define subcellular localization of RIN3 and to visualize endosomal changes in cultured primary BFCNs and PC12 cells.Recombinant flag-tagged RIN3 protein was purified from HEK293T cells and was used to define RIN3-interactomes by mass spectrometry.RIN3-interacting partners were validated by co-immunoprecipitation,immunofluorescence and yeast two hybrid assays.Live imaging of primary neurons was used to examine axonal transport of amyloid precursor protein(APP)andβ-secretase 1(BACE1).Immunoblotting was used to detect protein expression,processing of APP and phosphorylated forms of Tau.Results We have shown that RIN3 mRNA level was significantly increased in the hippocampus and cortex of APP/PS1 mouse brain.Basal forebrain cholinergic neurons(BFCNs)cultured from E18 APP/PS1 mouse embryos also showed increased RIN3 expression accompanied by early endosome enlargement.In addition,via its proline rich domain,RIN3 recruited BIN1(bridging integrator 1)and CD2AP(CD2 associated protein),two other AD risk factors,to early endosomes.Interestingly,overexpression of RIN3 or CD2AP promoted APP cleavage to increase its carboxyl terminal fragments(CTFs)in PC12 cells.Upregulation of RIN3 or the neuronal isoform of BIN1 increased phosphorylated Tau level.Therefore,upregulation of RIN3 expression promoted accumulation of APP CTFs and increased phosphorylated Tau.These effects by RIN3 was rescued by the expression of a dominant negative Rab5(Rab5S34N)construct.Our study has thus pointed to that RIN3 acts through Rab5 to impact endosomal trafficking and signaling.Conclusion RIN3 is significantly upregulated and correlated with endosomal dysfunction in APP/PS1 mouse.Through interacting with BIN1 and CD2AP,increased RIN3 expression alters axonal trafficking and procession of APP.Together with our previous studies,our current work has thus provided important insights into the role of RIN3 in regulating endosomal signaling and trafficking. | Ruinan Shen Xiaobei Zhao Lu He Yongbo Ding Wei Xu Suzhen Lin Savannah Fang Wanlin Yang Kijung Sung Brian Spencer Robert A.Rissman Ming Lei Jianqing Ding Chengbiao Wu | 2020 | Translational Neurodegeneration2020，9，2： | 1 |
| 5 | One at a time, live tracking of NGF axonal transport using quantum dots 显示文摘 | Bianxiao Cui Chengbiao Wu | 2007 | PNAS2007，104，13： | 1 |
| 6 | Cold air plasma:A potential strategy for inducing apoptosis of rheumatoid arthritis fibroblast‐like synoviocytes显示文摘Rheumatoid arthritis(RA)is an autoimmune disease of the joints characterised by synovial hyperplasia and chronic inflammation.Rheumatoid arthritis fibroblast‐like synoviocytes(RA‐FLS)cells are the dominant cell type in the hyperplastic synovial membrane,which play a key role in the pathogenesis of RA.They can invade cartilage,cause inflammation,destroy joints,and show tumour‐like anti‐apoptosis characteristics.Thus,the purpose of this study is to investigate the effect of cold air plasma(CAP)on RA‐FLS cells.The results showed that CAP treatment for 120 s could significantly reduce the viability of RA‐FLS cells,increase the content of intracellular reactive ox-ygen species(ROS),and significantly down‐regulate the ratio of apoptosis‐related protein Bcl‐2 to Bax.In this study,a novel approach of inducing apoptosis in RA‐FLS cells using CAP was proposed,which may provide a new choice for joint tar-geting therapy of RA. | Chengbiao Ding Chao Chen Wenchong Ouyang Qi Liu Lin Lin Zhengwei Wu | 2022 | High Voltage2022，7，1： | 0 |
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