Home > Publications Database > Oxidative and nitrative alpha-synuclein modifications and proteostatic stress: implications for disease mechanisms and interventions in synucleinopathies. > print

001     136890
005     20240321220144.0
024 7 _ |a 10.1111/jnc.12226
|2 doi
024 7 _ |a pmid:23452040
|2 pmid
024 7 _ |a 0022-3042
|2 ISSN
024 7 _ |a 1471-4159
|2 ISSN
037 _ _ |a DZNE-2020-03212
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Schildknecht, Stefan
|0 P:(DE-HGF)0
|b 0
|e Corresponding author
245 _ _ |a Oxidative and nitrative alpha-synuclein modifications and proteostatic stress: implications for disease mechanisms and interventions in synucleinopathies.
260 _ _ |a Oxford
|c 2013
|b Wiley-Blackwell
264 _ 1 |3 online
|2 Crossref
|b Wiley
|c 2013-03-19
264 _ 1 |3 print
|2 Crossref
|b Wiley
|c 2013-05-01
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1588853926_31742
|2 PUB:(DE-HGF)
|x Review Article
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a Alpha-synuclein (ASYN) is a major constituent of the typical protein aggregates observed in several neurodegenerative diseases that are collectively referred to as synucleinopathies. A causal involvement of ASYN in the initiation and progression of neurological diseases is suggested by observations indicating that single-point (e.g., A30P, A53T) or multiplication mutations of the gene encoding for ASYN cause early onset forms of Parkinson's disease (PD). The relative regional specificity of ASYN pathology is still a riddle that cannot be simply explained by its expression pattern. Also, transgenic over-expression of ASYN in mice does not recapitulate the typical dopaminergic neuronal death observed in PD. Thus, additional factors must contribute to ASYN-related toxicity. For instance, synucleinopathies are usually associated with inflammation and elevated levels of oxidative stress in affected brain areas. In turn, these conditions favor oxidative modifications of ASYN. Among these modifications, nitration of tyrosine residues, formation of covalent ASYN dimers, as well as methionine sulfoxidations are prominent examples that are observed in post-mortem PD brain sections. Oxidative modifications can affect ASYN aggregation, as well as its binding to biological membranes. This would affect neurotransmitter recycling, mitochondrial function and dynamics (fission/fusion), ASYN's degradation within a cell and, possibly, the transfer of modified ASYN to adjacent cells. Here, we propose a model on how covalent modifications of ASYN link energy stress, altered proteostasis, and oxidative stress, three major pathogenic processes involved in PD progression. Moreover, we hypothesize that ASYN may act physiologically as a catalytically regenerated scavenger of oxidants in healthy cells, thus performing an important protective role prior to the onset of disease or during aging.
536 _ _ |a 342 - Disease Mechanisms and Model Systems (POF3-342)
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|c POF3-342
|f POF III
|x 0
542 _ _ |i 2015-09-01
|2 Crossref
|u http://doi.wiley.com/10.1002/tdm_license_1.1
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a SNCA protein, human
|2 NLM Chemicals
650 _ 7 |a alpha-Synuclein
|2 NLM Chemicals
650 _ 7 |a Peroxynitrous Acid
|0 14691-52-2
|2 NLM Chemicals
650 _ 7 |a Nitric Oxide
|0 31C4KY9ESH
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Nerve Degeneration: metabolism
|2 MeSH
650 _ 2 |a Nerve Degeneration: pathology
|2 MeSH
650 _ 2 |a Nitric Oxide: metabolism
|2 MeSH
650 _ 2 |a Oxidative Stress: physiology
|2 MeSH
650 _ 2 |a Parkinson Disease: metabolism
|2 MeSH
650 _ 2 |a Parkinson Disease: pathology
|2 MeSH
650 _ 2 |a Peroxynitrous Acid: metabolism
|2 MeSH
650 _ 2 |a alpha-Synuclein: metabolism
|2 MeSH
700 1 _ |a Gerding, Hanne R
|b 1
700 1 _ |a Karreman, Christiaan
|b 2
700 1 _ |a Drescher, Malte
|b 3
700 1 _ |a Lashuel, Hilal A
|b 4
700 1 _ |a Outeiro, Tiago F
|0 P:(DE-HGF)0
|b 5
700 1 _ |a Di Monte, Donato A
|0 P:(DE-2719)2481741
|b 6
|u dzne
700 1 _ |a Leist, Marcel
|b 7
773 1 8 |a 10.1111/jnc.12226
|b : Wiley, 2013-03-19
|n 4
|p 491-511
|3 journal-article
|2 Crossref
|t Journal of Neurochemistry
|v 125
|y 2013
|x 0022-3042
773 _ _ |a 10.1111/jnc.12226
|g Vol. 125, no. 4, p. 491 - 511
|0 PERI:(DE-600)2020528-4
|n 4
|q 125:4<491 - 511
|p 491-511
|t Journal of neurochemistry
|v 125
|y 2013
|x 0022-3042
909 C O |o oai:pub.dzne.de:136890
|p VDB
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 6
|6 P:(DE-2719)2481741
913 1 _ |a DE-HGF
|b Forschungsbereich Gesundheit
|l Erkrankungen des Nervensystems
|1 G:(DE-HGF)POF3-340
|0 G:(DE-HGF)POF3-342
|2 G:(DE-HGF)POF3-300
|v Disease Mechanisms and Model Systems
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914 1 _ |y 2013
915 _ _ |a Nationallizenz
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|9 -- missing cx lookup --
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999 C 5 |a 10.1073/pnas.0406976102
|9 -- missing cx lookup --
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999 C 5 |a 10.1038/nm1746
|9 -- missing cx lookup --
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|9 -- missing cx lookup --
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|o 10.1002/mds.23012
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|o 10.1038/nature11557
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|9 -- missing cx lookup --
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|o 10.1074/jbc.M109.061051
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|o 10.1074/jbc.M205518200
999 C 5 |a 10.1523/JNEUROSCI.1746-05.2005
|9 -- missing cx lookup --
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|o 10.1523/JNEUROSCI.1746-05.2005
999 C 5 |a 10.1073/pnas.0908005106
|9 -- missing cx lookup --
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|o 10.1073/pnas.0908005106
999 C 5 |a 10.1126/science.1227157
|9 -- missing cx lookup --
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|o 10.1126/science.1227157
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|9 -- missing cx lookup --
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|o 10.1084/jem.20112457
999 C 5 |a 10.1074/jbc.M109.035774
|9 -- missing cx lookup --
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|o 10.1074/jbc.M109.035774
999 C 5 |a 10.1021/ja00139a027
|9 -- missing cx lookup --
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|o 10.1021/ja00139a027
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|9 -- missing cx lookup --
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|o 10.1074/jbc.M109.074617
999 C 5 |a 10.1021/bi300642h
|9 -- missing cx lookup --
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|9 -- missing cx lookup --
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|o 10.1021/ja312415q
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999 C 5 |a 10.1016/j.neuron.2005.05.010
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|9 -- missing cx lookup --
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|o 10.1074/jbc.M704737200
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|9 -- missing cx lookup --
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|o 10.1097/NEN.0b013e318180f0bd
999 C 5 |a 10.1371/journal.pone.0012122
|9 -- missing cx lookup --
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|o 10.1371/journal.pone.0012122
999 C 5 |a 10.1038/cddis.2012.50
|9 -- missing cx lookup --
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|o 10.1038/cddis.2012.50
999 C 5 |a 10.1021/tx980043h
|9 -- missing cx lookup --
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|o 10.1021/tx980043h
999 C 5 |a 10.3727/000000007783464911
|9 -- missing cx lookup --
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|o 10.3727/000000007783464911
999 C 5 |a 10.1021/bi047846q
|9 -- missing cx lookup --
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|o 10.1021/bi047846q
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|9 -- missing cx lookup --
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999 C 5 |a 10.1016/j.bbapap.2004.09.003
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.bbapap.2004.09.003
999 C 5 |a 10.1523/JNEUROSCI.20-09-03214.2000
|9 -- missing cx lookup --
|2 Crossref
|o 10.1523/JNEUROSCI.20-09-03214.2000
999 C 5 |a 10.1074/jbc.M110.213538
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.M110.213538
999 C 5 |a 10.1016/S0140-6736(10)62345-8
|9 -- missing cx lookup --
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|o 10.1016/S0140-6736(10)62345-8
999 C 5 |a 10.1021/bi002952n
|9 -- missing cx lookup --
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|o 10.1021/bi002952n
999 C 5 |a 10.1074/jbc.274.14.9843
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.274.14.9843
999 C 5 |a 10.1016/j.freeradbiomed.2010.11.027
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.freeradbiomed.2010.11.027
999 C 5 |a 10.1371/journal.pone.0027230
|9 -- missing cx lookup --
|2 Crossref
|o 10.1371/journal.pone.0027230
999 C 5 |a 10.1016/j.neuron.2009.12.023
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.neuron.2009.12.023
999 C 5 |a 10.1074/jbc.M412621200
|9 -- missing cx lookup --
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|o 10.1074/jbc.M412621200
999 C 5 |a 10.1126/science.1056784
|9 -- missing cx lookup --
|2 Crossref
|o 10.1126/science.1056784
999 C 5 |a 10.1074/jbc.M401076200
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.M401076200
999 C 5 |a 10.1093/hmg/6.10.1687
|9 -- missing cx lookup --
|2 Crossref
|o 10.1093/hmg/6.10.1687
999 C 5 |a 10.1002/ana.410320703
|9 -- missing cx lookup --
|2 Crossref
|o 10.1002/ana.410320703
999 C 5 |a 10.1016/S0079-6123(10)83007-9
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/S0079-6123(10)83007-9
999 C 5 |a 10.1126/science.1090439
|9 -- missing cx lookup --
|2 Crossref
|o 10.1126/science.1090439
999 C 5 |a 10.1074/jbc.M800747200
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.M800747200
999 C 5 |a 10.1523/JNEUROSCI.5922-09.2010
|9 -- missing cx lookup --
|2 Crossref
|o 10.1523/JNEUROSCI.5922-09.2010
999 C 5 |a 10.1038/srep00898
|9 -- missing cx lookup --
|2 Crossref
|o 10.1038/srep00898
999 C 5 |a 10.1007/s00018-008-7589-1
|9 -- missing cx lookup --
|2 Crossref
|o 10.1007/s00018-008-7589-1
999 C 5 |a 10.1074/jbc.275.9.6346
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.275.9.6346
999 C 5 |a 10.1126/science.274.5290.1197
|9 -- missing cx lookup --
|2 Crossref
|o 10.1126/science.274.5290.1197
999 C 5 |a 10.1126/science.276.5321.2045
|9 -- missing cx lookup --
|2 Crossref
|o 10.1126/science.276.5321.2045
999 C 5 |a 10.1016/0003-9861(85)90780-5
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/0003-9861(85)90780-5
999 C 5 |a 10.1074/jbc.M608126200
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.M608126200
999 C 5 |a 10.1073/pnas.87.24.10043
|9 -- missing cx lookup --
|2 Crossref
|o 10.1073/pnas.87.24.10043
999 C 5 |a 10.1111/j.1471-4159.2007.05087.x
|9 -- missing cx lookup --
|2 Crossref
|o 10.1111/j.1471-4159.2007.05087.x
999 C 5 |a 10.4049/jimmunol.0803982
|9 -- missing cx lookup --
|2 Crossref
|o 10.4049/jimmunol.0803982
999 C 5 |a 10.4049/jimmunol.0901852
|9 -- missing cx lookup --
|2 Crossref
|o 10.4049/jimmunol.0901852
999 C 5 |a 10.1002/cphc.201000815
|9 -- missing cx lookup --
|2 Crossref
|o 10.1002/cphc.201000815
999 C 5 |a 10.1021/bi300357a
|9 -- missing cx lookup --
|2 Crossref
|o 10.1021/bi300357a
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|9 -- missing cx lookup --
|2 Crossref
|o 10.1021/ja01195a022
999 C 5 |a 10.1016/j.mito.2012.05.002
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.mito.2012.05.002
999 C 5 |a 10.1016/j.molcel.2004.06.029
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.molcel.2004.06.029
999 C 5 |a 10.1111/j.1471-4159.1990.tb02325.x
|9 -- missing cx lookup --
|2 Crossref
|o 10.1111/j.1471-4159.1990.tb02325.x
999 C 5 |a 10.1016/j.abb.2008.10.023
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.abb.2008.10.023
999 C 5 |a 10.1096/fj.04-3465fje
|9 -- missing cx lookup --
|2 Crossref
|o 10.1096/fj.04-3465fje
999 C 5 |a 10.1074/jbc.M110.169565
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.M110.169565
999 C 5 |a 10.1089/ars.2011.4485
|9 -- missing cx lookup --
|2 Crossref
|o 10.1089/ars.2011.4485
999 C 5 |a 10.14573/altex.2012.3.261
|9 -- missing cx lookup --
|2 Crossref
|o 10.14573/altex.2012.3.261
999 C 5 |a 10.1111/j.1471-4159.2011.07255.x
|9 -- missing cx lookup --
|2 Crossref
|o 10.1111/j.1471-4159.2011.07255.x
999 C 5 |a 10.1016/j.neurobiolaging.2012.03.012
|9 -- missing cx lookup --
|2 Crossref
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|9 -- missing cx lookup --
|2 Crossref
|o 10.1523/JNEUROSCI.1091-10.2010
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|9 -- missing cx lookup --
|2 Crossref
|o 10.1021/ja2009554
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|9 -- missing cx lookup --
|2 Crossref
|o 10.1126/science.1090278
999 C 5 |a 10.1006/abbi.1999.1480
|9 -- missing cx lookup --
|2 Crossref
|o 10.1006/abbi.1999.1480
999 C 5 |a 10.1074/jbc.M000206200
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.M000206200
999 C 5 |a 10.1038/42166
|9 -- missing cx lookup --
|2 Crossref
|o 10.1038/42166
999 C 5 |a 10.1073/pnas.95.11.6469
|9 -- missing cx lookup --
|2 Crossref
|o 10.1073/pnas.95.11.6469
999 C 5 |a 10.1016/j.ajpath.2011.04.013
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.ajpath.2011.04.013
999 C 5 |a 10.1073/pnas.100110097
|9 -- missing cx lookup --
|2 Crossref
|o 10.1073/pnas.100110097
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|9 -- missing cx lookup --
|2 Crossref
|o 10.1039/C1MB05293D
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|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.neulet.2012.06.070
999 C 5 |a 10.1074/jbc.M503341200
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.M503341200
999 C 5 |a 10.1097/NEN.0b013e31818e5e99
|9 -- missing cx lookup --
|2 Crossref
|o 10.1097/NEN.0b013e31818e5e99
999 C 5 |a 10.1074/jbc.M308041200
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.M308041200
999 C 5 |a 10.1212/WNL.0b013e3181fd613b
|9 -- missing cx lookup --
|2 Crossref
|o 10.1212/WNL.0b013e3181fd613b
999 C 5 |y 2012
|2 Crossref
|o Ullrich 2012
999 C 5 |a 10.1074/jbc.M411805200
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.M411805200
999 C 5 |a 10.1007/s12035-012-8329-y
|9 -- missing cx lookup --
|2 Crossref
|o 10.1007/s12035-012-8329-y
999 C 5 |a 10.1111/j.1460-9568.2010.07284.x
|9 -- missing cx lookup --
|2 Crossref
|o 10.1111/j.1460-9568.2010.07284.x
999 C 5 |a 10.1006/abbi.1996.0131
|9 -- missing cx lookup --
|2 Crossref
|o 10.1006/abbi.1996.0131
999 C 5 |a 10.2174/138920309789351921
|9 -- missing cx lookup --
|2 Crossref
|o 10.2174/138920309789351921
999 C 5 |a 10.1074/jbc.M010907200
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.M010907200
999 C 5 |a 10.1074/jbc.C100551200
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.C100551200
999 C 5 |a 10.1016/S0014-5793(02)02638-8
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/S0014-5793(02)02638-8
999 C 5 |a 10.1016/j.molbrainres.2004.11.014
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.molbrainres.2004.11.014
999 C 5 |a 10.1016/j.jmb.2009.03.021
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.jmb.2009.03.021
999 C 5 |a 10.1002/path.2682
|9 -- missing cx lookup --
|2 Crossref
|o 10.1002/path.2682
999 C 5 |a 10.1016/S0140-6736(88)91161-0
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/S0140-6736(88)91161-0
999 C 5 |a 10.1006/abbi.1995.1303
|9 -- missing cx lookup --
|2 Crossref
|o 10.1006/abbi.1995.1303
999 C 5 |a 10.1074/jbc.M801992200
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.M801992200
999 C 5 |a 10.1021/bi0102398
|9 -- missing cx lookup --
|2 Crossref
|o 10.1021/bi0102398
999 C 5 |a 10.1016/j.neuron.2011.08.033
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.neuron.2011.08.033
999 C 5 |a 10.1523/JNEUROSCI.0322-07.2007
|9 -- missing cx lookup --
|2 Crossref
|o 10.1523/JNEUROSCI.0322-07.2007
999 C 5 |a 10.1126/science.1090389
|9 -- missing cx lookup --
|2 Crossref
|o 10.1126/science.1090389
999 C 5 |a 10.1073/pnas.1100976108
|9 -- missing cx lookup --
|2 Crossref
|o 10.1073/pnas.1100976108
999 C 5 |a 10.1074/jbc.M605965200
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.M605965200
999 C 5 |a 10.1074/jbc.274.28.19509
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.274.28.19509
999 C 5 |a 10.1371/journal.pone.0005515
|9 -- missing cx lookup --
|2 Crossref
|o 10.1371/journal.pone.0005515
999 C 5 |a 10.1016/S0014-5793(03)00367-3
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/S0014-5793(03)00367-3
999 C 5 |a 10.1126/science.1166088
|9 -- missing cx lookup --
|2 Crossref
|o 10.1126/science.1166088
999 C 5 |a 10.1523/JNEUROSCI.2559-04.2004
|9 -- missing cx lookup --
|2 Crossref
|o 10.1523/JNEUROSCI.2559-04.2004
999 C 5 |a 10.1073/pnas.0308215100
|9 -- missing cx lookup --
|2 Crossref
|o 10.1073/pnas.0308215100
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|9 -- missing cx lookup --
|2 Crossref
|o 10.1073/pnas.93.7.2696
999 C 5 |a 10.1126/science.1219855
|9 -- missing cx lookup --
|2 Crossref
|o 10.1126/science.1219855
999 C 5 |a 10.1002/ana.10795
|9 -- missing cx lookup --
|2 Crossref
|o 10.1002/ana.10795
999 C 5 |a 10.1096/fj.04-2751com
|9 -- missing cx lookup --
|2 Crossref
|o 10.1096/fj.04-2751com
999 C 5 |a 10.1016/j.jmb.2009.03.053
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.jmb.2009.03.053
999 C 5 |a 10.1016/j.bbadis.2009.12.004
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.bbadis.2009.12.004
999 C 5 |a 10.1074/jbc.M210136200
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.M210136200
999 C 5 |a 10.1074/jbc.M403129200
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.M403129200

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21