Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and alpha-synuclein mutations promote Tau protein phosphorylation at Ser262 and destabilize microtubule cytoskeleton in vitro.
Identifieur interne : 000B75 ( PubMed/Checkpoint ); précédent : 000B74; suivant : 000B76Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and alpha-synuclein mutations promote Tau protein phosphorylation at Ser262 and destabilize microtubule cytoskeleton in vitro.
Auteurs : Hamid Y. Qureshi [Canada] ; Hemant K. PaudelSource :
- The Journal of biological chemistry [ 1083-351X ] ; 2011.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology), Amino Acid Substitution, Cell Line, Tumor, Cyclic AMP-Dependent Protein Kinases (genetics), Cyclic AMP-Dependent Protein Kinases (metabolism), Genome-Wide Association Study, HEK293 Cells, Humans, Microtubules (genetics), Microtubules (metabolism), Mutation, Missense, Neurotoxins (pharmacology), Phosphorylation (drug effects), Phosphorylation (genetics), alpha-Synuclein (genetics), alpha-Synuclein (metabolism), tau Proteins (genetics), tau Proteins (metabolism).
- MESH :
- chemical , genetics : Cyclic AMP-Dependent Protein Kinases, alpha-Synuclein, tau Proteins.
- chemical , metabolism : Cyclic AMP-Dependent Protein Kinases, alpha-Synuclein, tau Proteins.
- chemical , pharmacology : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Neurotoxins.
- drug effects : Phosphorylation.
- genetics : Microtubules, Phosphorylation.
- metabolism : Microtubules.
- Amino Acid Substitution, Cell Line, Tumor, Genome-Wide Association Study, HEK293 Cells, Humans, Mutation, Missense.
Abstract
In Parkinson disease (PD) brain, a progressive loss of dopaminergic neurons leads to dopamine depletion in the striatum and reduced motor function. Lewy bodies, the characteristic neuropathological lesions found in the brain of PD patients, are composed mainly of α-synuclein protein. Three point mutations in the α-synuclein gene are associated with familial PD. In addition, genome-wide association studies indicate that α-synuclein and Tau protein synergistically increase disease susceptibility in the human population. To determine the mechanism by which α-synuclein and Tau act together, we have used PD-causing neurotoxin MPTP and pathogenic α-synuclein mutants A30P, E46K, and A53T as models. We found that exposure of human neuroblastoma M17 cells to MPTP enhances the intracellular α-synuclein protein level, stimulates Tau protein phosphorylation at Ser(262), and induces apoptosis. In mouse brain, ablation of α-synuclein function significantly suppresses Tau phosphorylation at Ser(262). In vitro, α-synuclein binds to phosphorylated Ser(214) of Tau and stimulates PKA-catalyzed Tau phosphorylation at Ser(262). PD-associated α-synuclein mutations increase α-synuclein binding to Tau and stimulate Tau phosphorylation at Ser(262). In HEK-293 cells, α-synuclein and its all PD-associated mutants destabilize the microtubule cytoskeleton in a similar extent. In contrast, when co-expressed with Tau, these PD-associated mutants destabilize microtubules with significantly higher potency than WT. Our results demonstrate that α-synuclein is an in vivo regulator of Tau protein phosphorylation at Ser(262) and suggest that PD-associated risk factors such as environmental toxins and α-synuclein mutations promote Tau phosphorylation at Ser(262), causing microtubule instability, which leads to loss of dopaminergic neurons in PD brain.
DOI: 10.1074/jbc.M110.178905
PubMed: 21127069
Affiliations:
Links toward previous steps (curation, corpus...)
Links to Exploration step
pubmed:21127069Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and alpha-synuclein mutations promote Tau protein phosphorylation at Ser262 and destabilize microtubule cytoskeleton in vitro.</title><author><name sortKey="Qureshi, Hamid Y" sort="Qureshi, Hamid Y" uniqKey="Qureshi H" first="Hamid Y" last="Qureshi">Hamid Y. Qureshi</name><affiliation wicri:level="4"><nlm:affiliation>Department of Neurology and Neurosurgery, McGill University, Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neurology and Neurosurgery, McGill University, Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec H3T 1E2</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Paudel, Hemant K" sort="Paudel, Hemant K" uniqKey="Paudel H" first="Hemant K" last="Paudel">Hemant K. Paudel</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2011">2011</date><idno type="RBID">pubmed:21127069</idno><idno type="pmid">21127069</idno><idno type="doi">10.1074/jbc.M110.178905</idno><idno type="wicri:Area/PubMed/Corpus">000C46</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000C46</idno><idno type="wicri:Area/PubMed/Curation">000C46</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000C46</idno><idno type="wicri:Area/PubMed/Checkpoint">000C46</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000C46</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and alpha-synuclein mutations promote Tau protein phosphorylation at Ser262 and destabilize microtubule cytoskeleton in vitro.</title><author><name sortKey="Qureshi, Hamid Y" sort="Qureshi, Hamid Y" uniqKey="Qureshi H" first="Hamid Y" last="Qureshi">Hamid Y. Qureshi</name><affiliation wicri:level="4"><nlm:affiliation>Department of Neurology and Neurosurgery, McGill University, Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Neurology and Neurosurgery, McGill University, Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec H3T 1E2</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Paudel, Hemant K" sort="Paudel, Hemant K" uniqKey="Paudel H" first="Hemant K" last="Paudel">Hemant K. Paudel</name></author></analytic><series><title level="j">The Journal of biological chemistry</title><idno type="eISSN">1083-351X</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology)</term><term>Amino Acid Substitution</term><term>Cell Line, Tumor</term><term>Cyclic AMP-Dependent Protein Kinases (genetics)</term><term>Cyclic AMP-Dependent Protein Kinases (metabolism)</term><term>Genome-Wide Association Study</term><term>HEK293 Cells</term><term>Humans</term><term>Microtubules (genetics)</term><term>Microtubules (metabolism)</term><term>Mutation, Missense</term><term>Neurotoxins (pharmacology)</term><term>Phosphorylation (drug effects)</term><term>Phosphorylation (genetics)</term><term>alpha-Synuclein (genetics)</term><term>alpha-Synuclein (metabolism)</term><term>tau Proteins (genetics)</term><term>tau Proteins (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Cyclic AMP-Dependent Protein Kinases</term><term>alpha-Synuclein</term><term>tau Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cyclic AMP-Dependent Protein Kinases</term><term>alpha-Synuclein</term><term>tau Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>Neurotoxins</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Phosphorylation</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Microtubules</term><term>Phosphorylation</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Microtubules</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Amino Acid Substitution</term><term>Cell Line, Tumor</term><term>Genome-Wide Association Study</term><term>HEK293 Cells</term><term>Humans</term><term>Mutation, Missense</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In Parkinson disease (PD) brain, a progressive loss of dopaminergic neurons leads to dopamine depletion in the striatum and reduced motor function. Lewy bodies, the characteristic neuropathological lesions found in the brain of PD patients, are composed mainly of α-synuclein protein. Three point mutations in the α-synuclein gene are associated with familial PD. In addition, genome-wide association studies indicate that α-synuclein and Tau protein synergistically increase disease susceptibility in the human population. To determine the mechanism by which α-synuclein and Tau act together, we have used PD-causing neurotoxin MPTP and pathogenic α-synuclein mutants A30P, E46K, and A53T as models. We found that exposure of human neuroblastoma M17 cells to MPTP enhances the intracellular α-synuclein protein level, stimulates Tau protein phosphorylation at Ser(262), and induces apoptosis. In mouse brain, ablation of α-synuclein function significantly suppresses Tau phosphorylation at Ser(262). In vitro, α-synuclein binds to phosphorylated Ser(214) of Tau and stimulates PKA-catalyzed Tau phosphorylation at Ser(262). PD-associated α-synuclein mutations increase α-synuclein binding to Tau and stimulate Tau phosphorylation at Ser(262). In HEK-293 cells, α-synuclein and its all PD-associated mutants destabilize the microtubule cytoskeleton in a similar extent. In contrast, when co-expressed with Tau, these PD-associated mutants destabilize microtubules with significantly higher potency than WT. Our results demonstrate that α-synuclein is an in vivo regulator of Tau protein phosphorylation at Ser(262) and suggest that PD-associated risk factors such as environmental toxins and α-synuclein mutations promote Tau phosphorylation at Ser(262), causing microtubule instability, which leads to loss of dopaminergic neurons in PD brain.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">21127069</PMID><DateCreated><Year>2011</Year><Month>02</Month><Day>14</Day></DateCreated><DateCompleted><Year>2011</Year><Month>04</Month><Day>11</Day></DateCompleted><DateRevised><Year>2016</Year><Month>10</Month><Day>19</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1083-351X</ISSN><JournalIssue CitedMedium="Internet"><Volume>286</Volume><Issue>7</Issue><PubDate><Year>2011</Year><Month>Feb</Month><Day>18</Day></PubDate></JournalIssue><Title>The Journal of biological chemistry</Title><ISOAbbreviation>J. Biol. Chem.</ISOAbbreviation></Journal><ArticleTitle>Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and alpha-synuclein mutations promote Tau protein phosphorylation at Ser262 and destabilize microtubule cytoskeleton in vitro.</ArticleTitle><Pagination><MedlinePgn>5055-68</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1074/jbc.M110.178905</ELocationID><Abstract><AbstractText>In Parkinson disease (PD) brain, a progressive loss of dopaminergic neurons leads to dopamine depletion in the striatum and reduced motor function. Lewy bodies, the characteristic neuropathological lesions found in the brain of PD patients, are composed mainly of α-synuclein protein. Three point mutations in the α-synuclein gene are associated with familial PD. In addition, genome-wide association studies indicate that α-synuclein and Tau protein synergistically increase disease susceptibility in the human population. To determine the mechanism by which α-synuclein and Tau act together, we have used PD-causing neurotoxin MPTP and pathogenic α-synuclein mutants A30P, E46K, and A53T as models. We found that exposure of human neuroblastoma M17 cells to MPTP enhances the intracellular α-synuclein protein level, stimulates Tau protein phosphorylation at Ser(262), and induces apoptosis. In mouse brain, ablation of α-synuclein function significantly suppresses Tau phosphorylation at Ser(262). In vitro, α-synuclein binds to phosphorylated Ser(214) of Tau and stimulates PKA-catalyzed Tau phosphorylation at Ser(262). PD-associated α-synuclein mutations increase α-synuclein binding to Tau and stimulate Tau phosphorylation at Ser(262). In HEK-293 cells, α-synuclein and its all PD-associated mutants destabilize the microtubule cytoskeleton in a similar extent. In contrast, when co-expressed with Tau, these PD-associated mutants destabilize microtubules with significantly higher potency than WT. Our results demonstrate that α-synuclein is an in vivo regulator of Tau protein phosphorylation at Ser(262) and suggest that PD-associated risk factors such as environmental toxins and α-synuclein mutations promote Tau phosphorylation at Ser(262), causing microtubule instability, which leads to loss of dopaminergic neurons in PD brain.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Qureshi</LastName><ForeName>Hamid Y</ForeName><Initials>HY</Initials><AffiliationInfo><Affiliation>Department of Neurology and Neurosurgery, McGill University, Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Paudel</LastName><ForeName>Hemant K</ForeName><Initials>HK</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><Agency>Canadian Institutes of Health Research</Agency><Country>Canada</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2010</Year><Month>12</Month><Day>02</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>J Biol Chem</MedlineTA><NlmUniqueID>2985121R</NlmUniqueID><ISSNLinking>0021-9258</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C054369">MAPT protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D009498">Neurotoxins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051844">alpha-Synuclein</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D016875">tau Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>9P21XSP91P</RegistryNumber><NameOfSubstance UI="D015632">1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.11</RegistryNumber><NameOfSubstance UI="D017868">Cyclic AMP-Dependent Protein Kinases</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Neuron. 1993 Jul;11(1):153-63</RefSource><PMID Version="1">8393323</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5562-6</RefSource><PMID Version="1">8202528</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 1995 Jan 13;270(2):823-9</RefSource><PMID Version="1">7822317</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R188-95</RefSource><PMID Version="1">16987883</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>FASEB J. 2006 Nov;20(13):2302-12</RefSource><PMID Version="1">17077307</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Ann Neurol. 2007 Aug;62(2):145-53</RefSource><PMID Version="1">17683088</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):15136-41</RefSource><PMID Version="1">18812510</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Neurochem. 2008 Oct;107(2):303-16</RefSource><PMID Version="1">18691382</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Neurochem. 2009 Jan;108(1):33-43</RefSource><PMID Version="1">19014373</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Trends Mol Med. 2009 Mar;15(3):112-9</RefSource><PMID Version="1">19246243</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2009 May 15;284(20):13422-33</RefSource><PMID Version="1">19304664</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Biochim Biophys Acta. 2009 Jul;1792(7):616-24</RefSource><PMID Version="1">18955133</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Neurochem. 2009 Jul;110(2):719-33</RefSource><PMID Version="1">19457084</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>FASEB J. 2009 Sep;23(9):2820-30</RefSource><PMID Version="1">19369384</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Rev Drug Discov. 2009 Oct;8(10):783-93</RefSource><PMID Version="1">19794442</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Neurosci. 2009 Oct 14;29(41):12994-3005</RefSource><PMID Version="1">19828813</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Genet. 2009 Dec;41(12):1308-12</RefSource><PMID Version="1">19915575</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Genet. 2009 Dec;41(12):1303-7</RefSource><PMID Version="1">19915576</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Mol Biol Rep. 2010 Oct;37(7):3183-92</RefSource><PMID Version="1">19826908</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Neurochem. 2000 Feb;74(2):721-9</RefSource><PMID Version="1">10646524</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Science. 2000 Feb 18;287(5456):1265-9</RefSource><PMID Version="1">10678833</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Neurochem. 2000 Apr;74(4):1587-95</RefSource><PMID Version="1">10737616</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nature. 2000 Mar 23;404(6776):394-8</RefSource><PMID Version="1">10746727</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Annu Rev Neurosci. 2001;24:1121-59</RefSource><PMID Version="1">11520930</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2002 Apr 5;277(14):11933-40</RefSource><PMID Version="1">11812770</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Med. 2002 Jun;8(6):600-6</RefSource><PMID Version="1">12042811</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Neuron. 2002 May 16;34(4):521-33</RefSource><PMID Version="1">12062037</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Acta Neuropathol. 2002 Jul;104(1):7-11</RefSource><PMID Version="1">12070658</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8968-73</RefSource><PMID Version="1">12084935</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Proc Natl Acad Sci U S A. 2002 Oct 29;99(22):14524-9</RefSource><PMID Version="1">12376616</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Eur J Neurosci. 2003 Jan;17(1):1-12</RefSource><PMID Version="1">12534964</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Science. 2003 Apr 25;300(5619):636-40</RefSource><PMID Version="1">12714745</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Neuropathol Exp Neurol. 2003 Apr;62(4):389-97</RefSource><PMID Version="1">12722831</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Biochemistry. 2003 Jul 22;42(28):8530-40</RefSource><PMID Version="1">12859200</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Acta Neuropathol. 2003 Sep;106(3):243-50</RefSource><PMID Version="1">12811584</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Cell. 2004 Mar 5;116(5):671-82</RefSource><PMID Version="1">15006350</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Trends Neurosci. 2004 Mar;27(3):129-34</RefSource><PMID Version="1">15036877</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2002 Jan 18;277(3):2112-7</RefSource><PMID Version="1">11698390</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 1995 Mar 3;270(9):4854-60</RefSource><PMID Version="1">7876258</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 1995 Aug 11;270(32):18917-22</RefSource><PMID Version="1">7642549</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 1997 Jan 17;272(3):1777-85</RefSource><PMID Version="1">8999860</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Ann Neurol. 1997 Feb;41(2):277-81</RefSource><PMID Version="1">9029080</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Science. 1997 Jun 27;276(5321):2045-7</RefSource><PMID Version="1">9197268</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Genet. 1998 Feb;18(2):106-8</RefSource><PMID Version="1">9462735</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Hum Mol Genet. 1999 Apr;8(4):711-5</RefSource><PMID Version="1">10072441</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 1999 Mar 19;274(12):7619-22</RefSource><PMID Version="1">10075647</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 1999 Jul 9;274(28):19509-12</RefSource><PMID Version="1">10391881</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Neurosci. 1999 Jul 15;19(14):5782-91</RefSource><PMID Version="1">10407019</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 1999 Sep 3;274(36):25481-9</RefSource><PMID Version="1">10464279</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Brain Res. 1999 Oct 2;843(1-2):53-61</RefSource><PMID Version="1">10528110</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Exp Neurol. 2005 Apr;192(2):244-50</RefSource><PMID Version="1">15755542</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Exp Neurol. 2005 Apr;192(2):274-87</RefSource><PMID Version="1">15755545</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Brain Res Mol Brain Res. 2005 Mar 24;134(1):57-66</RefSource><PMID Version="1">15790530</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5215-20</RefSource><PMID Version="1">15784737</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Hum Mol Genet. 2005 Aug 15;14(16):2399-404</RefSource><PMID Version="1">16000317</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>FEBS Lett. 2005 Aug 29;579(21):4781-6</RefSource><PMID Version="1">16098973</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 2005 Oct 7;280(40):34105-12</RefSource><PMID Version="1">16091364</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Neurosci. 2006 Jan 4;26(1):41-50</RefSource><PMID Version="1">16399671</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Nat Rev Neurosci. 2006 Mar;7(3):207-19</RefSource><PMID Version="1">16495942</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Exp Neurol. 2004 Jun;187(2):279-88</RefSource><PMID Version="1">15144854</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Neurotoxicology. 2004 Sep;25(5):761-9</RefSource><PMID Version="1">15288507</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Ann Neurol. 1980 Apr;7(4):329-35</RefSource><PMID Version="1">7377758</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Methods Enzymol. 1988;159:159-72</RefSource><PMID Version="1">2842582</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 1990 Jun 25;265(18):10484-91</RefSource><PMID Version="1">2162349</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Biol Chem. 1993 Jan 15;268(2):1166-73</RefSource><PMID Version="1">8419321</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D015632" MajorTopicYN="N">1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D019943" MajorTopicYN="N">Amino Acid Substitution</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D045744" MajorTopicYN="N">Cell Line, Tumor</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017868" MajorTopicYN="N">Cyclic AMP-Dependent Protein Kinases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D055106" MajorTopicYN="N">Genome-Wide Association Study</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D057809" MajorTopicYN="N">HEK293 Cells</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008870" MajorTopicYN="N">Microtubules</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020125" MajorTopicYN="Y">Mutation, Missense</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009498" MajorTopicYN="N">Neurotoxins</DescriptorName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010766" MajorTopicYN="N">Phosphorylation</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051844" MajorTopicYN="N">alpha-Synuclein</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D016875" MajorTopicYN="N">tau Proteins</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="N">genetics</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading></MeshHeadingList><OtherID Source="NLM">PMC3037617</OtherID></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2010</Year><Month>12</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2010</Year><Month>12</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2011</Year><Month>4</Month><Day>13</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">21127069</ArticleId><ArticleId IdType="pii">M110.178905</ArticleId><ArticleId IdType="doi">10.1074/jbc.M110.178905</ArticleId><ArticleId IdType="pmc">PMC3037617</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li></country><region><li>Québec</li></region><settlement><li>Montréal</li></settlement><orgName><li>Université McGill</li></orgName></list><tree><noCountry><name sortKey="Paudel, Hemant K" sort="Paudel, Hemant K" uniqKey="Paudel H" first="Hemant K" last="Paudel">Hemant K. Paudel</name></noCountry><country name="Canada"><region name="Québec"><name sortKey="Qureshi, Hamid Y" sort="Qureshi, Hamid Y" uniqKey="Qureshi H" first="Hamid Y" last="Qureshi">Hamid Y. Qureshi</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/PubMed/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000B75 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd -nk 000B75 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= PubMed
|étape= Checkpoint
|type= RBID
|clé= pubmed:21127069
|texte= Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and alpha-synuclein mutations promote Tau protein phosphorylation at Ser262 and destabilize microtubule cytoskeleton in vitro.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/PubMed/Checkpoint/RBID.i -Sk "pubmed:21127069" \
| HfdSelect -Kh $EXPLOR_AREA/Data/PubMed/Checkpoint/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonCanadaV1
| This area was generated with Dilib version V0.6.29. |  |