Amanda M Haidet-Phillips, Mark E Hester, Carlos J Miranda, Kathrin Meyer, Lyndsey Braun, Ashley Frakes, SungWon Song, Shibi Likhite, Matthew J Murtha, Kevin D Foust, Meghan Rao, Amy Eagle, Anja Kammesheidt, Ashley Christensen, Jerry R Mendell, Arthur H M Burghes, Brian K Kaspar. Nat Biotechnol 2011
Times Cited: 527
Times Cited: 527
Times Cited
Times Co-cited
Similarity
Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons.
Makiko Nagai, Diane B Re, Tetsuya Nagata, Alcmène Chalazonitis, Thomas M Jessell, Hynek Wichterle, Serge Przedborski. Nat Neurosci 2007
Makiko Nagai, Diane B Re, Tetsuya Nagata, Alcmène Chalazonitis, Thomas M Jessell, Hynek Wichterle, Serge Przedborski. Nat Neurosci 2007
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Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis.
Koji Yamanaka, Seung Joo Chun, Severine Boillee, Noriko Fujimori-Tonou, Hirofumi Yamashita, David H Gutmann, Ryosuke Takahashi, Hidemi Misawa, Don W Cleveland. Nat Neurosci 2008
Koji Yamanaka, Seung Joo Chun, Severine Boillee, Noriko Fujimori-Tonou, Hirofumi Yamashita, David H Gutmann, Ryosuke Takahashi, Hidemi Misawa, Don W Cleveland. Nat Neurosci 2008
33
Neurotoxic reactive astrocytes are induced by activated microglia.
Shane A Liddelow, Kevin A Guttenplan, Laura E Clarke, Frederick C Bennett, Christopher J Bohlen, Lucas Schirmer, Mariko L Bennett, Alexandra E Münch, Won-Suk Chung, Todd C Peterson,[...]. Nature 2017
Shane A Liddelow, Kevin A Guttenplan, Laura E Clarke, Frederick C Bennett, Christopher J Bohlen, Lucas Schirmer, Mariko L Bennett, Alexandra E Münch, Won-Suk Chung, Todd C Peterson,[...]. Nature 2017
31
Direct conversion of patient fibroblasts demonstrates non-cell autonomous toxicity of astrocytes to motor neurons in familial and sporadic ALS.
Kathrin Meyer, Laura Ferraiuolo, Carlos J Miranda, Shibi Likhite, Sohyun McElroy, Samantha Renusch, Dara Ditsworth, Clotilde Lagier-Tourenne, Richard A Smith, John Ravits,[...]. Proc Natl Acad Sci U S A 2014
Kathrin Meyer, Laura Ferraiuolo, Carlos J Miranda, Shibi Likhite, Sohyun McElroy, Samantha Renusch, Dara Ditsworth, Clotilde Lagier-Tourenne, Richard A Smith, John Ravits,[...]. Proc Natl Acad Sci U S A 2014
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Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model.
Francesco Paolo Di Giorgio, Monica A Carrasco, Michelle C Siao, Tom Maniatis, Kevin Eggan. Nat Neurosci 2007
Francesco Paolo Di Giorgio, Monica A Carrasco, Michelle C Siao, Tom Maniatis, Kevin Eggan. Nat Neurosci 2007
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24
Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis.
D R Rosen, T Siddique, D Patterson, D A Figlewicz, P Sapp, A Hentati, D Donaldson, J Goto, J P O'Regan, H X Deng. Nature 1993
D R Rosen, T Siddique, D Patterson, D A Figlewicz, P Sapp, A Hentati, D Donaldson, J Goto, J P O'Regan, H X Deng. Nature 1993
24
Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation.
M E Gurney, H Pu, A Y Chiu, M C Dal Canto, C Y Polchow, D D Alexander, J Caliendo, A Hentati, Y W Kwon, H X Deng. Science 1994
M E Gurney, H Pu, A Y Chiu, M C Dal Canto, C Y Polchow, D D Alexander, J Caliendo, A Hentati, Y W Kwon, H X Deng. Science 1994
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Onset and progression in inherited ALS determined by motor neurons and microglia.
Séverine Boillée, Koji Yamanaka, Christian S Lobsiger, Neal G Copeland, Nancy A Jenkins, George Kassiotis, George Kollias, Don W Cleveland. Science 2006
Séverine Boillée, Koji Yamanaka, Christian S Lobsiger, Neal G Copeland, Nancy A Jenkins, George Kassiotis, George Kollias, Don W Cleveland. Science 2006
22
Necroptosis drives motor neuron death in models of both sporadic and familial ALS.
Diane B Re, Virginia Le Verche, Changhao Yu, Mackenzie W Amoroso, Kristin A Politi, Sudarshan Phani, Burcin Ikiz, Lucas Hoffmann, Martijn Koolen, Tetsuya Nagata,[...]. Neuron 2014
Diane B Re, Virginia Le Verche, Changhao Yu, Mackenzie W Amoroso, Kristin A Politi, Sudarshan Phani, Burcin Ikiz, Lucas Hoffmann, Martijn Koolen, Tetsuya Nagata,[...]. Neuron 2014
20
Microglia induce motor neuron death via the classical NF-κB pathway in amyotrophic lateral sclerosis.
Ashley E Frakes, Laura Ferraiuolo, Amanda M Haidet-Phillips, Leah Schmelzer, Lyndsey Braun, Carlos J Miranda, Katherine J Ladner, Adam K Bevan, Kevin D Foust, Jonathan P Godbout,[...]. Neuron 2014
Ashley E Frakes, Laura Ferraiuolo, Amanda M Haidet-Phillips, Leah Schmelzer, Lyndsey Braun, Carlos J Miranda, Katherine J Ladner, Adam K Bevan, Kevin D Foust, Jonathan P Godbout,[...]. Neuron 2014
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Human iPSC-derived astrocytes from ALS patients with mutated C9ORF72 show increased oxidative stress and neurotoxicity.
Anastasya Birger, Israel Ben-Dor, Miri Ottolenghi, Tikva Turetsky, Yaniv Gil, Sahar Sweetat, Liat Perez, Vitali Belzer, Natania Casden, Debora Steiner,[...]. EBioMedicine 2019
Anastasya Birger, Israel Ben-Dor, Miri Ottolenghi, Tikva Turetsky, Yaniv Gil, Sahar Sweetat, Liat Perez, Vitali Belzer, Natania Casden, Debora Steiner,[...]. EBioMedicine 2019
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Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.
Manuela Neumann, Deepak M Sampathu, Linda K Kwong, Adam C Truax, Matthew C Micsenyi, Thomas T Chou, Jennifer Bruce, Theresa Schuck, Murray Grossman, Christopher M Clark,[...]. Science 2006
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Sporadic ALS Astrocytes Induce Neuronal Degeneration In Vivo.
Kun Qian, Hailong Huang, Andrew Peterson, Baoyang Hu, Nicholas J Maragakis, Guo-Li Ming, Hong Chen, Su-Chun Zhang. Stem Cell Reports 2017
Kun Qian, Hailong Huang, Andrew Peterson, Baoyang Hu, Nicholas J Maragakis, Guo-Li Ming, Hong Chen, Su-Chun Zhang. Stem Cell Reports 2017
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Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy.
Andrea Serio, Bilada Bilican, Sami J Barmada, Dale Michael Ando, Chen Zhao, Rick Siller, Karen Burr, Ghazal Haghi, David Story, Agnes Lumi Nishimura,[...]. Proc Natl Acad Sci U S A 2013
Andrea Serio, Bilada Bilican, Sami J Barmada, Dale Michael Ando, Chen Zhao, Rick Siller, Karen Burr, Ghazal Haghi, David Story, Agnes Lumi Nishimura,[...]. Proc Natl Acad Sci U S A 2013
17
Astrocyte loss of mutant SOD1 delays ALS disease onset and progression in G85R transgenic mice.
Lijun Wang, David H Gutmann, Raymond P Roos. Hum Mol Genet 2011
Lijun Wang, David H Gutmann, Raymond P Roos. Hum Mol Genet 2011
17
Non-cell-autonomous effect of human SOD1 G37R astrocytes on motor neurons derived from human embryonic stem cells.
Maria C N Marchetto, Alysson R Muotri, Yangling Mu, Alan M Smith, Gabriela G Cezar, Fred H Gage. Cell Stem Cell 2008
Maria C N Marchetto, Alysson R Muotri, Yangling Mu, Alan M Smith, Gabriela G Cezar, Fred H Gage. Cell Stem Cell 2008
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Amyotrophic lateral sclerosis patient iPSC-derived astrocytes impair autophagy via non-cell autonomous mechanisms.
Martin Madill, Katya McDonagh, Jun Ma, Alice Vajda, Paul McLoughlin, Timothy O'Brien, Orla Hardiman, Sanbing Shen. Mol Brain 2017
Martin Madill, Katya McDonagh, Jun Ma, Alice Vajda, Paul McLoughlin, Timothy O'Brien, Orla Hardiman, Sanbing Shen. Mol Brain 2017
21
Reactive Astrocytes Promote ALS-like Degeneration and Intracellular Protein Aggregation in Human Motor Neurons by Disrupting Autophagy through TGF-β1.
Pratibha Tripathi, Natalia Rodriguez-Muela, Joseph R Klim, A Sophie de Boer, Sahil Agrawal, Jackson Sandoe, Claudia S Lopes, Karolyn Sassi Ogliari, Luis A Williams, Matthew Shear,[...]. Stem Cell Reports 2017
Pratibha Tripathi, Natalia Rodriguez-Muela, Joseph R Klim, A Sophie de Boer, Sahil Agrawal, Jackson Sandoe, Claudia S Lopes, Karolyn Sassi Ogliari, Luis A Williams, Matthew Shear,[...]. Stem Cell Reports 2017
25
Micro-RNAs secreted through astrocyte-derived extracellular vesicles cause neuronal network degeneration in C9orf72 ALS.
André Varcianna, Monika A Myszczynska, Lydia M Castelli, Brendan O'Neill, Yeseul Kim, Jordan Talbot, Sophie Nyberg, Immanuelle Nyamali, Paul R Heath, Matthew J Stopford,[...]. EBioMedicine 2019
André Varcianna, Monika A Myszczynska, Lydia M Castelli, Brendan O'Neill, Yeseul Kim, Jordan Talbot, Sophie Nyberg, Immanuelle Nyamali, Paul R Heath, Matthew J Stopford,[...]. EBioMedicine 2019
19
Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease.
Angelo C Lepore, Britta Rauck, Christine Dejea, Andrea C Pardo, Mahendra S Rao, Jeffrey D Rothstein, Nicholas J Maragakis. Nat Neurosci 2008
Angelo C Lepore, Britta Rauck, Christine Dejea, Andrea C Pardo, Mahendra S Rao, Jeffrey D Rothstein, Nicholas J Maragakis. Nat Neurosci 2008
15
Genomic analysis of reactive astrogliosis.
Jennifer L Zamanian, Lijun Xu, Lynette C Foo, Navid Nouri, Lu Zhou, Rona G Giffard, Ben A Barres. J Neurosci 2012
Jennifer L Zamanian, Lijun Xu, Lynette C Foo, Navid Nouri, Lu Zhou, Rona G Giffard, Ben A Barres. J Neurosci 2012
15
Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model.
Kevin A Guttenplan, Maya K Weigel, Drew I Adler, Julien Couthouis, Shane A Liddelow, Aaron D Gitler, Ben A Barres. Nat Commun 2020
Kevin A Guttenplan, Maya K Weigel, Drew I Adler, Julien Couthouis, Shane A Liddelow, Aaron D Gitler, Ben A Barres. Nat Commun 2020
26
Astrocytes expressing mutant SOD1 and TDP43 trigger motoneuron death that is mediated via sodium channels and nitroxidative stress.
Fabiola Rojas, Nicole Cortes, Sebastian Abarzua, Agnieszka Dyrda, Brigitte van Zundert. Front Cell Neurosci 2014
Fabiola Rojas, Nicole Cortes, Sebastian Abarzua, Agnieszka Dyrda, Brigitte van Zundert. Front Cell Neurosci 2014
19
Astrocytes carrying the superoxide dismutase 1 (SOD1G93A) mutation induce wild-type motor neuron degeneration in vivo.
Sophia T Papadeas, Sarah E Kraig, Colin O'Banion, Angelo C Lepore, Nicholas J Maragakis. Proc Natl Acad Sci U S A 2011
Sophia T Papadeas, Sarah E Kraig, Colin O'Banion, Angelo C Lepore, Nicholas J Maragakis. Proc Natl Acad Sci U S A 2011
14
14
Wild-type microglia extend survival in PU.1 knockout mice with familial amyotrophic lateral sclerosis.
David R Beers, Jenny S Henkel, Qin Xiao, Weihua Zhao, Jinghong Wang, Albert A Yen, Laszlo Siklos, Scott R McKercher, Stanley H Appel. Proc Natl Acad Sci U S A 2006
David R Beers, Jenny S Henkel, Qin Xiao, Weihua Zhao, Jinghong Wang, Albert A Yen, Laszlo Siklos, Scott R McKercher, Stanley H Appel. Proc Natl Acad Sci U S A 2006
14
Human embryonic stem cell-derived motor neurons are sensitive to the toxic effect of glial cells carrying an ALS-causing mutation.
Francesco Paolo Di Giorgio, Gabriella L Boulting, Samuel Bobrowicz, Kevin C Eggan. Cell Stem Cell 2008
Francesco Paolo Di Giorgio, Gabriella L Boulting, Samuel Bobrowicz, Kevin C Eggan. Cell Stem Cell 2008
13
Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS.
Mariely DeJesus-Hernandez, Ian R Mackenzie, Bradley F Boeve, Adam L Boxer, Matt Baker, Nicola J Rutherford, Alexandra M Nicholson, NiCole A Finch, Heather Flynn, Jennifer Adamson,[...]. Neuron 2011
Mariely DeJesus-Hernandez, Ian R Mackenzie, Bradley F Boeve, Adam L Boxer, Matt Baker, Nicola J Rutherford, Alexandra M Nicholson, NiCole A Finch, Heather Flynn, Jennifer Adamson,[...]. Neuron 2011
13
Neuroinflammation in amyotrophic lateral sclerosis: role of glial activation in motor neuron disease.
Thomas Philips, Wim Robberecht. Lancet Neurol 2011
Thomas Philips, Wim Robberecht. Lancet Neurol 2011
13
ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions.
L I Bruijn, M W Becher, M K Lee, K L Anderson, N A Jenkins, N G Copeland, S S Sisodia, J D Rothstein, D R Borchelt, D L Price,[...]. Neuron 1997
L I Bruijn, M W Becher, M K Lee, K L Anderson, N A Jenkins, N G Copeland, S S Sisodia, J D Rothstein, D R Borchelt, D L Price,[...]. Neuron 1997
13
Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice.
A M Clement, M D Nguyen, E A Roberts, M L Garcia, S Boillée, M Rule, A P McMahon, W Doucette, D Siwek, R J Ferrante,[...]. Science 2003
A M Clement, M D Nguyen, E A Roberts, M L Garcia, S Boillée, M Rule, A P McMahon, W Doucette, D Siwek, R J Ferrante,[...]. Science 2003
13
Normal aging induces A1-like astrocyte reactivity.
Laura E Clarke, Shane A Liddelow, Chandrani Chakraborty, Alexandra E Münch, Myriam Heiman, Ben A Barres. Proc Natl Acad Sci U S A 2018
Laura E Clarke, Shane A Liddelow, Chandrani Chakraborty, Alexandra E Münch, Myriam Heiman, Ben A Barres. Proc Natl Acad Sci U S A 2018
13
Expression of ALS-linked TDP-43 mutant in astrocytes causes non-cell-autonomous motor neuron death in rats.
Jianbin Tong, Cao Huang, Fangfang Bi, Qinxue Wu, Bo Huang, Xionghao Liu, Fang Li, Hongxia Zhou, Xu-Gang Xia. EMBO J 2013
Jianbin Tong, Cao Huang, Fangfang Bi, Qinxue Wu, Bo Huang, Xionghao Liu, Fang Li, Hongxia Zhou, Xu-Gang Xia. EMBO J 2013
12
TDP-43 activates microglia through NF-κB and NLRP3 inflammasome.
Weihua Zhao, David R Beers, Shaughn Bell, Jinghong Wang, Shixiang Wen, Robert H Baloh, Stanley H Appel. Exp Neurol 2015
Weihua Zhao, David R Beers, Shaughn Bell, Jinghong Wang, Shixiang Wen, Robert H Baloh, Stanley H Appel. Exp Neurol 2015
12
Astrocyte-derived TGF-β1 accelerates disease progression in ALS mice by interfering with the neuroprotective functions of microglia and T cells.
Fumito Endo, Okiru Komine, Noriko Fujimori-Tonou, Masahisa Katsuno, Shijie Jin, Seiji Watanabe, Gen Sobue, Mari Dezawa, Tony Wyss-Coray, Koji Yamanaka. Cell Rep 2015
Fumito Endo, Okiru Komine, Noriko Fujimori-Tonou, Masahisa Katsuno, Shijie Jin, Seiji Watanabe, Gen Sobue, Mari Dezawa, Tony Wyss-Coray, Koji Yamanaka. Cell Rep 2015
12
Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis.
Shin H Kang, Ying Li, Masahiro Fukaya, Ileana Lorenzini, Don W Cleveland, Lyle W Ostrow, Jeffrey D Rothstein, Dwight E Bergles. Nat Neurosci 2013
Shin H Kang, Ying Li, Masahiro Fukaya, Ileana Lorenzini, Don W Cleveland, Lyle W Ostrow, Jeffrey D Rothstein, Dwight E Bergles. Nat Neurosci 2013
12
Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis.
Pablo Díaz-Amarilla, Silvia Olivera-Bravo, Emiliano Trias, Andrea Cragnolini, Laura Martínez-Palma, Patricia Cassina, Joseph Beckman, Luis Barbeito. Proc Natl Acad Sci U S A 2011
Pablo Díaz-Amarilla, Silvia Olivera-Bravo, Emiliano Trias, Andrea Cragnolini, Laura Martínez-Palma, Patricia Cassina, Joseph Beckman, Luis Barbeito. Proc Natl Acad Sci U S A 2011
12
State of play in amyotrophic lateral sclerosis genetics.
Alan E Renton, Adriano Chiò, Bryan J Traynor. Nat Neurosci 2014
Alan E Renton, Adriano Chiò, Bryan J Traynor. Nat Neurosci 2014
12
A Unique Microglia Type Associated with Restricting Development of Alzheimer's Disease.
Hadas Keren-Shaul, Amit Spinrad, Assaf Weiner, Orit Matcovitch-Natan, Raz Dvir-Szternfeld, Tyler K Ulland, Eyal David, Kuti Baruch, David Lara-Astaiso, Beata Toth,[...]. Cell 2017
Hadas Keren-Shaul, Amit Spinrad, Assaf Weiner, Orit Matcovitch-Natan, Raz Dvir-Szternfeld, Tyler K Ulland, Eyal David, Kuti Baruch, David Lara-Astaiso, Beata Toth,[...]. Cell 2017
12
TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis.
Jemeen Sreedharan, Ian P Blair, Vineeta B Tripathi, Xun Hu, Caroline Vance, Boris Rogelj, Steven Ackerley, Jennifer C Durnall, Kelly L Williams, Emanuele Buratti,[...]. Science 2008
Jemeen Sreedharan, Ian P Blair, Vineeta B Tripathi, Xun Hu, Caroline Vance, Boris Rogelj, Steven Ackerley, Jennifer C Durnall, Kelly L Williams, Emanuele Buratti,[...]. Science 2008
11
Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond.
Hristelina Ilieva, Magdalini Polymenidou, Don W Cleveland. J Cell Biol 2009
Hristelina Ilieva, Magdalini Polymenidou, Don W Cleveland. J Cell Biol 2009
11
Mutant C9orf72 human iPSC-derived astrocytes cause non-cell autonomous motor neuron pathophysiology.
Chen Zhao, Anna-Claire Devlin, Amit K Chouhan, Bhuvaneish T Selvaraj, Maria Stavrou, Karen Burr, Veronica Brivio, Xin He, Arpan R Mehta, David Story,[...]. Glia 2020
Chen Zhao, Anna-Claire Devlin, Amit K Chouhan, Bhuvaneish T Selvaraj, Maria Stavrou, Karen Burr, Veronica Brivio, Xin He, Arpan R Mehta, David Story,[...]. Glia 2020
23
11
C9orf72 is required for proper macrophage and microglial function in mice.
J G O'Rourke, L Bogdanik, A Yáñez, D Lall, A J Wolf, A K M G Muhammad, R Ho, S Carmona, J P Vit, J Zarrow,[...]. Science 2016
J G O'Rourke, L Bogdanik, A Yáñez, D Lall, A J Wolf, A K M G Muhammad, R Ho, S Carmona, J P Vit, J Zarrow,[...]. Science 2016
11
Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS).
David S Howland, Jian Liu, Yijin She, Beth Goad, Nicholas J Maragakis, Benjamin Kim, Jamie Erickson, John Kulik, Lisa DeVito, George Psaltis,[...]. Proc Natl Acad Sci U S A 2002
David S Howland, Jian Liu, Yijin She, Beth Goad, Nicholas J Maragakis, Benjamin Kim, Jamie Erickson, John Kulik, Lisa DeVito, George Psaltis,[...]. Proc Natl Acad Sci U S A 2002
11
Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study.
M R Turner, A Cagnin, F E Turkheimer, C C J Miller, C E Shaw, D J Brooks, P N Leigh, R B Banati. Neurobiol Dis 2004
M R Turner, A Cagnin, F E Turkheimer, C C J Miller, C E Shaw, D J Brooks, P N Leigh, R B Banati. Neurobiol Dis 2004
10
Transformation from a neuroprotective to a neurotoxic microglial phenotype in a mouse model of ALS.
Bing Liao, Weihua Zhao, David R Beers, Jenny S Henkel, Stanley H Appel. Exp Neurol 2012
Bing Liao, Weihua Zhao, David R Beers, Jenny S Henkel, Stanley H Appel. Exp Neurol 2012
10
Progressive Motor Neuron Pathology and the Role of Astrocytes in a Human Stem Cell Model of VCP-Related ALS.
Claire E Hall, Zhi Yao, Minee Choi, Giulia E Tyzack, Andrea Serio, Raphaelle Luisier, Jasmine Harley, Elisavet Preza, Charlie Arber, Sarah J Crisp,[...]. Cell Rep 2017
Claire E Hall, Zhi Yao, Minee Choi, Giulia E Tyzack, Andrea Serio, Raphaelle Luisier, Jasmine Harley, Elisavet Preza, Charlie Arber, Sarah J Crisp,[...]. Cell Rep 2017
12
Converging mechanisms in ALS and FTD: disrupted RNA and protein homeostasis.
Shuo-Chien Ling, Magdalini Polymenidou, Don W Cleveland. Neuron 2013
Shuo-Chien Ling, Magdalini Polymenidou, Don W Cleveland. Neuron 2013
10
Co-cited is the co-citation frequency, indicating how many articles cite the article together with the query article. Similarity is the co-citation as percentage of the times cited of the query article or the article in the search results, whichever is the lowest. These numbers are calculated for the last 100 citations when articles are cited more than 100 times.