喵ID：sxa8f5
BIN1 protein isoforms are differentially expressed in astrocytes, neurons, and microglia: neuronal and astrocyte BIN1 implicated in Tau pathology BIN1 protein isoforms are differentially expressed in astrocytes, neurons, and microglia: neuronal and astrocyte BIN1 implicated in Tau pathology
BIN1 protein isoforms are differentially expressed in astrocytes, neurons, and microglia: neuronal and astrocyte BIN1 implicated in Tau pathology
BIN1 protein isoforms are differentially expressed in astrocytes, neurons, and microglia: neuronal and astrocyte BIN1 implicated in Tau pathologyBIN1 蛋白亚型在星形胶质细胞、神经元和小胶质细胞中差异表达：神经元和星形胶质细胞 BIN1 与 Tau 病理有关
基本信息
DOI：
10.1101/535682
10.1101/535682发表时间：
2019
2019期刊：
bioRxiv
bioRxiv影响因子：
--
--通讯作者：
P. D. De Jager
P. D. De Jager中科院分区：
文献类型：
--
-- 作者： M. Taga;V. Petyuk;Charles C. White;Galina Marsh;Yiyi Ma;Hans Klein;Sarah M. Connor;Anthony Khairallah;M. Olah;J. Schneider;Richard M Ransohoff;David A. Bennett;Andrea Crotti;Elizabeth M Bradshaw;P. D. De Jager
研究方向： --
MeSH主题词： --
关键词： --
来源链接：pubmed详情页地址
文献摘要
Identified as an Alzheimer’s disease (AD) susceptibility gene by genome wide-association studies, BIN1 has 10 isoforms that are expressed in the Central Nervous System (CNS). The distribution of these isoforms in different cell types, as well as their role in AD pathology still remains unclear. Utilizing antibodies targeting specific BIN1 epitopes in human postmortem tissue and analyzing RNA expression data from purified microglia, we identified three isoforms expressed specifically in neurons (isoforms 1, 2 and 3) and four isoforms expressed in microglia (isoforms 6, 9, 10 and 12). The abundance of selected peptides, which correspond to groups of BIN1 protein isoforms, was measured in dorsolateral prefrontal cortex, and their relation to neuropathological features of AD was assessed. Peptides contained in exon 7 of BIN1’s N-BAR domain were found to be significantly associated with AD-related traits and, particularly, tau pathology. Since only isoforms 1, 2 and 3 contain exon 7, it appears that decreased protein expression of the N-BAR domain of BIN1 is associated with greater accumulation of tau pathology and subsequent cognitive decline, with astrocytic rather than neuronal BIN1 being the more likely culprit. These effects are independent of the BIN1 AD risk variant, suggesting that targeting specific BIN1 isoforms might be a novel therapeutic approach to prevent the accumulation of tau pathology.
通过全基因组关联研究被确定为阿尔茨海默病（AD）易感基因，BIN1有10种异构体，它们在中枢神经系统（CNS）中表达。这些异构体在不同细胞类型中的分布以及它们在AD病理学中的作用仍然不清楚。利用针对人死后组织中特定BIN1表位的抗体，并分析来自纯化小胶质细胞的RNA表达数据，我们确定了三种在神经元中特异性表达的异构体（异构体1、2和3）以及四种在小胶质细胞中表达的异构体（异构体6、9、10和12）。在背外侧前额叶皮质中测量了与BIN1蛋白异构体组相对应的选定肽的丰度，并评估了它们与AD神经病理学特征的关系。发现BIN1的N - BAR结构域第7外显子中包含的肽与AD相关特征，特别是tau病理学显著相关。由于只有异构体1、2和3包含第7外显子，似乎BIN1的N - BAR结构域的蛋白质表达降低与tau病理学的更大积累以及随后的认知下降相关，而星形胶质细胞的BIN1而非神经元的BIN1更可能是罪魁祸首。这些效应与BIN1的AD风险变体无关，这表明针对特定的BIN1异构体可能是一种预防tau病理学积累的新型治疗方法。
参考文献（8）
被引文献（1）
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10.1001/jama.2010.574
10.1001/jama.2010.574发表时间：
2010-05-12
2010-05-12期刊：
影响因子：
120.7
120.7作者：
Seshadri, Sudha;Fitzpatrick, Annette L.;Ikram, M. Arfan;DeStefano, Anita L.;Gudnason, Vilmundur;Boada, Merce;Bis, Joshua C.;Smith, Albert V.;Carassquillo, Minerva M.;Lambert, Jean Charles;Harold, Denise;Schrijvers, Elisabeth M. C.;Ramirez-Lorca, Reposo;Debette, Stephanie;Longstreth, W. T., Jr.;Janssens, A. Cecile J. W.;Pankratz, V. Shane;Dartigues, Jean Francois;Hollingworth, Paul;Aspelund, Thor;Hernandez, Isabel;Beiser, Alexa;Kuller, Lewis H.;Koudstaal, Peter J.;Dickson, Dennis W.;Tzourio, Christophe;Abraham, Richard;Antunez, Carmen;Du, Yangchun;Rotter, Jerome I.;Aulchenko, Yurii S.;Harris, Tamara B.;Petersen, Ronald C.;Berr, Claudine;Owen, Michael J.;Lopez-Arrieta, Jesus;Varadarajan, Badri N.;Becker, James T.;Rivadeneira, Fernando;Nalls, Michael A.;Graff-Radford, Neill R.;Campion, Dominique;Auerbach, Sanford;Rice, Kenneth;Hofman, Albert;Jonsson, Palmi V.;Schmidt, Helena;Lathrop, Mark;Mosley, Thomas H.;Au, Rhoda;Psaty, Bruce M.;Uitterlinden, Andre G.;Farrer, Lindsay A.;Lumley, Thomas;Ruiz, Agustin;Williams, Julie;Amouyel, Philippe;Younkin, Steve G.;Wolf, Philip A.;Launer, Lenore J.;Lopez, Oscar L.;van Duijn, Cornelia M.;Breteler, Monique M. B.
Seshadri, Sudha;Fitzpatrick, Annette L.;Ikram, M. Arfan;DeStefano, Anita L.;Gudnason, Vilmundur;Boada, Merce;Bis, Joshua C.;Smith, Albert V.;Carassquillo, Minerva M.;Lambert, Jean Charles;Harold, Denise;Schrijvers, Elisabeth M. C.;Ramirez-Lorca, Reposo;Debette, Stephanie;Longstreth, W. T., Jr.;Janssens, A. Cecile J. W.;Pankratz, V. Shane;Dartigues, Jean Francois;Hollingworth, Paul;Aspelund, Thor;Hernandez, Isabel;Beiser, Alexa;Kuller, Lewis H.;Koudstaal, Peter J.;Dickson, Dennis W.;Tzourio, Christophe;Abraham, Richard;Antunez, Carmen;Du, Yangchun;Rotter, Jerome I.;Aulchenko, Yurii S.;Harris, Tamara B.;Petersen, Ronald C.;Berr, Claudine;Owen, Michael J.;Lopez-Arrieta, Jesus;Varadarajan, Badri N.;Becker, James T.;Rivadeneira, Fernando;Nalls, Michael A.;Graff-Radford, Neill R.;Campion, Dominique;Auerbach, Sanford;Rice, Kenneth;Hofman, Albert;Jonsson, Palmi V.;Schmidt, Helena;Lathrop, Mark;Mosley, Thomas H.;Au, Rhoda;Psaty, Bruce M.;Uitterlinden, Andre G.;Farrer, Lindsay A.;Lumley, Thomas;Ruiz, Agustin;Williams, Julie;Amouyel, Philippe;Younkin, Steve G.;Wolf, Philip A.;Launer, Lenore J.;Lopez, Oscar L.;van Duijn, Cornelia M.;Breteler, Monique M. B.通讯作者：
Breteler, Monique M. B.
Breteler, Monique M. B.Bin1 ablation increases susceptibility to cancer during aging, particularly lung cancer
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10.1158/0008-5472.can-07-1100
10.1158/0008-5472.can-07-1100发表时间：
2007-08-15
2007-08-15影响因子：
11.2
11.2作者：
Chang, Mee Young;Boulden, Janette;Prendergast, George C.
Chang, Mee Young;Boulden, Janette;Prendergast, George C.通讯作者：
Prendergast, George C.
Prendergast, George C.Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.DOI：
10.1038/ng.2802
10.1038/ng.2802发表时间：
2013-12
2013-12影响因子：
30.8
30.8作者：
Lambert, Jean-Charles;Ibrahim-Verbaas, Carla A.;Harold, Denise;Naj, Adam C.;Sims, Rebecca;Bellenguez, Celine;Jun, Gyungah;DeStefano, Anita L.;Bis, Joshua C.;Beecham, Gary W.;Grenier-Boley, Benjamin;Russo, Giancarlo;Thornton-Wells, Tricia A.;Jones, Nicola;Smith, Albert V.;Chouraki, Vincent;Thomas, Charlene;Ikram, M. Arfan;Zelenika, Diana;Vardarajan, Badri N.;Kamatani, Yoichiro;Lin, Chiao-Feng;Gerrish, Amy;Schmidt, Helena;Kunkle, Brian;Dunstan, Melanie L.;Ruiz, Agustin;Bihoreau, Marie-Therese;Choi, Seung-Hoan;Reitz, Christiane;Pasquier, Florence;Hollingworth, Paul;Ramirez, Alfredo;Hanon, Olivier;Fitzpatrick, Annette L.;Buxbaum, Joseph D.;Campion, Dominique;Crane, Paul K.;Baldwin, Clinton;Becker, Tim;Gudnason, Vilmundur;Cruchaga, Carlos;Craig, David;Amin, Najaf;Berr, Claudine;Lopez, Oscar L.;De Jager, Philip L.;Deramecourt, Vincent;Johnston, Janet A.;Evans, Denis;Lovestone, Simon;Letenneur, Luc;Moron, Francisco J.;Rubinsztein, David C.;Eiriksdottir, Gudny;Sleegers, Kristel;Goate, Alison M.;Fievet, Nathalie;Huentelman, Matthew J.;Gill, Michael;Brown, Kristelle;Kamboh, M. Ilyas;Keller, Lina;Barberger-Gateau, Pascale;McGuinness, Bernadette;Larson, Eric B.;Green, Robert;Myers, Amanda J.;Dufouil, Carole;Todd, Stephen;Wallon, David;Love, Seth;Rogaeva, Ekaterina;Gallacher, John;St George-Hyslop, Peter;Clarimon, Jordi;Lleo, Alberto;Bayer, Anthony;Tsuang, Debby W.;Yu, Lei;Tsolaki, Magda;Bossu, Paola;Spalletta, Gianfranco;Proitsi, Petroula;Collinge, John;Sorbi, Sandro;Sanchez-Garcia, Florentino;Fox, Nick C.;Hardy, John;Naranjo, Maria Candida Deniz;Bosco, Paolo;Clarke, Robert;Brayne, Carol;Galimberti, Daniela;Mancuso, Michelangelo;Matthews, Fiona;Moebus, Susanne;Mecocci, Patrizia;Del Zompo, Maria;Maier, Wolfgang;Hampel, Harald;Pilotto, Alberto;Bullido, Maria;Panza, Francesco;Caffarra, Paolo;Nacmias, Benedetta;Gilbert, John R.;Mayhaus, Manuel;Lannfelt, Lars;Hakonarson, Hakon;Pichler, Sabrina;Carrasquillo, Minerva M.;Ingelsson, Martin;Beekly, Duane;Alvarez, Victoria;Zou, Fanggeng;Valladares, Otto;Younkin, Steven G.;Coto, Eliecer;Hamilton-Nelson, Kara L.;Gu, Wei;Razquin, Cristina;Pastor, Pau;Mateo, Ignacio;Owen, Michael J.;Faber, Kelley M.;Jonsson, Palmi V.;Combarros, Onofre;O'Donovan, Michael C.;Cantwell, Laura B.;Soininen, Hilkka;Blacker, Deborah;Mead, Simon;Mosley, Thomas H., Jr.;Bennett, David A.;Harris, Tamara B.;Fratiglioni, Laura;Holmes, Clive;de Bruijn, Renee F. A. G.;Passmore, Peter;Montine, Thomas J.;Bettens, Karolien;Rotter, Jerome I.;Brice, Alexis;Morgan, Kevin;Foroud, Tatiana M.;Kukull, Walter A.;Hannequin, Didier;Powell, John F.;Nalls, Michael A.;Ritchie, Karen;Lunetta, Kathryn L.;Kauwe, John S. K.;Boerwinkle, Eric;Riemenschneider, Matthias;Boada, Merce;Hiltunen, Mikko;Martin, Eden R.;Schmidt, Reinhold;Rujescu, Dan;Wang, Li-San;Dartigues, Jean-Francois;Mayeux, Richard;Tzourio, Christophe;Hofman, Albert;Noethen, Markus M.;Graff, Caroline;Psaty, Bruce M.;Jones, Lesley;Haines, Jonathan L.;Holmans, Peter A.;Lathrop, Mark;Pericak-Vance, Margaret A.;Launer, Lenore J.;Farrer, Lindsay A.;van Duijn, Cornelia M.;Van Broeckhoven, Christine;Moskvina, Valentina;Seshadri, Sudha;Williams, Julie;Schellenberg, Gerard D.;Amouyel, Philippe
Lambert, Jean-Charles;Ibrahim-Verbaas, Carla A.;Harold, Denise;Naj, Adam C.;Sims, Rebecca;Bellenguez, Celine;Jun, Gyungah;DeStefano, Anita L.;Bis, Joshua C.;Beecham, Gary W.;Grenier-Boley, Benjamin;Russo, Giancarlo;Thornton-Wells, Tricia A.;Jones, Nicola;Smith, Albert V.;Chouraki, Vincent;Thomas, Charlene;Ikram, M. Arfan;Zelenika, Diana;Vardarajan, Badri N.;Kamatani, Yoichiro;Lin, Chiao-Feng;Gerrish, Amy;Schmidt, Helena;Kunkle, Brian;Dunstan, Melanie L.;Ruiz, Agustin;Bihoreau, Marie-Therese;Choi, Seung-Hoan;Reitz, Christiane;Pasquier, Florence;Hollingworth, Paul;Ramirez, Alfredo;Hanon, Olivier;Fitzpatrick, Annette L.;Buxbaum, Joseph D.;Campion, Dominique;Crane, Paul K.;Baldwin, Clinton;Becker, Tim;Gudnason, Vilmundur;Cruchaga, Carlos;Craig, David;Amin, Najaf;Berr, Claudine;Lopez, Oscar L.;De Jager, Philip L.;Deramecourt, Vincent;Johnston, Janet A.;Evans, Denis;Lovestone, Simon;Letenneur, Luc;Moron, Francisco J.;Rubinsztein, David C.;Eiriksdottir, Gudny;Sleegers, Kristel;Goate, Alison M.;Fievet, Nathalie;Huentelman, Matthew J.;Gill, Michael;Brown, Kristelle;Kamboh, M. Ilyas;Keller, Lina;Barberger-Gateau, Pascale;McGuinness, Bernadette;Larson, Eric B.;Green, Robert;Myers, Amanda J.;Dufouil, Carole;Todd, Stephen;Wallon, David;Love, Seth;Rogaeva, Ekaterina;Gallacher, John;St George-Hyslop, Peter;Clarimon, Jordi;Lleo, Alberto;Bayer, Anthony;Tsuang, Debby W.;Yu, Lei;Tsolaki, Magda;Bossu, Paola;Spalletta, Gianfranco;Proitsi, Petroula;Collinge, John;Sorbi, Sandro;Sanchez-Garcia, Florentino;Fox, Nick C.;Hardy, John;Naranjo, Maria Candida Deniz;Bosco, Paolo;Clarke, Robert;Brayne, Carol;Galimberti, Daniela;Mancuso, Michelangelo;Matthews, Fiona;Moebus, Susanne;Mecocci, Patrizia;Del Zompo, Maria;Maier, Wolfgang;Hampel, Harald;Pilotto, Alberto;Bullido, Maria;Panza, Francesco;Caffarra, Paolo;Nacmias, Benedetta;Gilbert, John R.;Mayhaus, Manuel;Lannfelt, Lars;Hakonarson, Hakon;Pichler, Sabrina;Carrasquillo, Minerva M.;Ingelsson, Martin;Beekly, Duane;Alvarez, Victoria;Zou, Fanggeng;Valladares, Otto;Younkin, Steven G.;Coto, Eliecer;Hamilton-Nelson, Kara L.;Gu, Wei;Razquin, Cristina;Pastor, Pau;Mateo, Ignacio;Owen, Michael J.;Faber, Kelley M.;Jonsson, Palmi V.;Combarros, Onofre;O'Donovan, Michael C.;Cantwell, Laura B.;Soininen, Hilkka;Blacker, Deborah;Mead, Simon;Mosley, Thomas H., Jr.;Bennett, David A.;Harris, Tamara B.;Fratiglioni, Laura;Holmes, Clive;de Bruijn, Renee F. A. G.;Passmore, Peter;Montine, Thomas J.;Bettens, Karolien;Rotter, Jerome I.;Brice, Alexis;Morgan, Kevin;Foroud, Tatiana M.;Kukull, Walter A.;Hannequin, Didier;Powell, John F.;Nalls, Michael A.;Ritchie, Karen;Lunetta, Kathryn L.;Kauwe, John S. K.;Boerwinkle, Eric;Riemenschneider, Matthias;Boada, Merce;Hiltunen, Mikko;Martin, Eden R.;Schmidt, Reinhold;Rujescu, Dan;Wang, Li-San;Dartigues, Jean-Francois;Mayeux, Richard;Tzourio, Christophe;Hofman, Albert;Noethen, Markus M.;Graff, Caroline;Psaty, Bruce M.;Jones, Lesley;Haines, Jonathan L.;Holmans, Peter A.;Lathrop, Mark;Pericak-Vance, Margaret A.;Launer, Lenore J.;Farrer, Lindsay A.;van Duijn, Cornelia M.;Van Broeckhoven, Christine;Moskvina, Valentina;Seshadri, Sudha;Williams, Julie;Schellenberg, Gerard D.;Amouyel, Philippe通讯作者：
Amouyel, Philippe
Amouyel, PhilippeAn environment-dependent transcriptional network specifies human microglia identity.
An environment-dependent transcriptional network specifies human microglia identity.DOI：
10.1126/science.aal3222
10.1126/science.aal3222发表时间：
2017-06-23
2017-06-23影响因子：
0
0作者：
Gosselin D;Skola D;Coufal NG;Holtman IR;Schlachetzki JCM;Sajti E;Jaeger BN;O'Connor C;Fitzpatrick C;Pasillas MP;Pena M;Adair A;Gonda DD;Levy ML;Ransohoff RM;Gage FH;Glass CK
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Glass CK
Glass CKBAR, F-BAR (EFC) and ENTH/ANTH domains in the regulation of membrane-cytosol interfaces and membrane curvature
BAR, F-BAR (EFC) and ENTH/ANTH domains in the regulation of membrane-cytosol interfaces and membrane curvatureDOI：
10.1016/j.bbalip.2006.06.015
10.1016/j.bbalip.2006.06.015发表时间：
2006-08-01
2006-08-01影响因子：
4.8
4.8作者：
Itoh, Toshiki;De Camilli, Pietro
Itoh, Toshiki;De Camilli, Pietro通讯作者：
De Camilli, Pietro
De Camilli, Pietro共 7 条
- 1
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