Chronic administration of cholesterol oximes in mice increases transcription of cytoprotective genes and improves transcriptome alterations induced by alpha-synuclein overexpression in nigrostriatal dopaminergic neurons.
Identifieur interne : 000518 ( PubMed/Corpus ); précédent : 000517; suivant : 000519Chronic administration of cholesterol oximes in mice increases transcription of cytoprotective genes and improves transcriptome alterations induced by alpha-synuclein overexpression in nigrostriatal dopaminergic neurons.
Auteurs : Franziska Richter ; Fuying Gao ; Vera Medvedeva ; Patrick Lee ; Nicholas Bove ; Sheila M. Fleming ; Magali Michaud ; Vincent Lemesre ; Stefano Patassini ; Krystal De La Rosa ; Caitlin K. Mulligan ; Pedrom C. Sioshansi ; Chunni Zhu ; Giovanni Coppola ; Thierry Bordet ; Rebecca M. Pruss ; Marie-Françoise ChesseletSource :
- Neurobiology of disease [ 1095-953X ] ; 2014.
English descriptors
- KwdEn :
- Animals, Brain (drug effects), Brain (metabolism), Cholestenones (pharmacokinetics), Cholestenones (pharmacology), Corpus Striatum (drug effects), Corpus Striatum (metabolism), Dopamine Agonists (pharmacology), Dopaminergic Neurons (drug effects), Dopaminergic Neurons (metabolism), Gene Expression (drug effects), Humans, Male, Mice, Transgenic, Movement Disorders (drug therapy), Movement Disorders (metabolism), Neuroprotective Agents (pharmacokinetics), Neuroprotective Agents (pharmacology), Oximes (pharmacokinetics), Oximes (pharmacology), Parkinsonian Disorders (drug therapy), Parkinsonian Disorders (metabolism), RNA, Messenger (metabolism), Secosteroids (pharmacokinetics), Secosteroids (pharmacology), Substantia Nigra (drug effects), Substantia Nigra (metabolism), Transcriptome (drug effects), alpha-Synuclein (genetics), alpha-Synuclein (metabolism).
- MESH :
- chemical , genetics : alpha-Synuclein.
- chemical , metabolism : RNA, Messenger, alpha-Synuclein.
- chemical , pharmacokinetics : Cholestenones, Neuroprotective Agents, Oximes, Secosteroids.
- drug effects : Brain, Corpus Striatum, Dopaminergic Neurons, Gene Expression, Substantia Nigra, Transcriptome.
- drug therapy : Movement Disorders, Parkinsonian Disorders.
- metabolism : Brain, Corpus Striatum, Dopaminergic Neurons, Movement Disorders, Parkinsonian Disorders, Substantia Nigra.
- chemical , pharmacology : Cholestenones, Dopamine Agonists, Neuroprotective Agents, Oximes, Secosteroids.
- Animals, Humans, Male, Mice, Transgenic.
Abstract
Cholesterol-oximes TRO19622 and TRO40303 target outer mitochondrial membrane proteins and have beneficial effects in preclinical models of neurodegenerative diseases leading to their advancement to clinical trials. Dopaminergic neurons degenerate in Parkinson's disease (PD) and are prone to oxidative stress and mitochondrial dysfunction. In order to provide insights into the neuroprotective potential of TRO19622 and TRO40303 for dopaminergic neurons in vivo, we assessed their effects on gene expression in laser captured nigrostriatal dopaminergic neurons of wildtype mice and of mice that over-express alpha-synuclein, a protein involved in both familial and sporadic forms of PD (Thy1-aSyn mice). Young mice were fed the drugs in food pellets or a control diet from 1 to 4months of age, approximately 10months before the appearance of striatal dopamine loss in this model. Unbiased weighted gene co-expression network analysis (WGCNA) of transcriptional changes revealed effects of cholesterol oximes on transcripts related to mitochondria, cytoprotection and anti-oxidant response in wild-type and transgenic mice, including increased transcription of stress defense (e.g. Prdx1, Prdx2, Glrx2, Hspa9, Pink1, Drp1, Trak1) and dopamine-related (Th, Ddc, Gch1, Dat, Vmat2, Drd2, Chnr6a) genes. Even at this young age transgenic mice showed alterations in transcripts implicated in mitochondrial function and oxidative stress (e.g. Bcl-2, Bax, Casp3, Nos2), and both drugs normalized about 20% of these alterations. Young Thy1-aSyn mice exhibit motor deficits that differ from parkinsonism and are established before the onset of treatment; these deficits were not improved by cholesterol oximes. However, high doses of TRO40303 improved olfaction and produced the same effects as dopamine agonists on a challenging beam test, specifically an increase in footslips, an observation congruent with its effects on transcripts involved in dopamine synthesis. High doses of TRO19622 increased alpha-synuclein aggregates in the substantia nigra; this effect, not seen with TRO40303 was inconsistent and may represent a protective mechanism as in other neurodegenerative diseases. Overall, the results suggest that cholesterol oximes, while not improving early effects of alpha-synuclein overexpression on motor behavior or pathology, may ameliorate the function and resilience of dopaminergic neurons in vivo and support further studies of neuroprotection in models with dopaminergic cell loss.
DOI: 10.1016/j.nbd.2014.05.012
PubMed: 24844147
Links to Exploration step
pubmed:24844147Le document en format XML
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Parc Scientifique de Luminy, Case 931, 13288 Marseille Cedex 9, France.</nlm:affiliation></affiliation></author><author><name sortKey="Pruss, Rebecca M" sort="Pruss, Rebecca M" uniqKey="Pruss R" first="Rebecca M" last="Pruss">Rebecca M. Pruss</name><affiliation><nlm:affiliation>Trophos S.A. Parc Scientifique de Luminy, Case 931, 13288 Marseille Cedex 9, France.</nlm:affiliation></affiliation></author><author><name sortKey="Chesselet, Marie Francoise" sort="Chesselet, Marie Francoise" uniqKey="Chesselet M" first="Marie-Françoise" last="Chesselet">Marie-Françoise Chesselet</name><affiliation><nlm:affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA. Electronic address: mchesselet@mednet.ucla.edu.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24844147</idno><idno type="pmid">24844147</idno><idno type="doi">10.1016/j.nbd.2014.05.012</idno><idno type="wicri:Area/PubMed/Corpus">000518</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000518</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Chronic administration of cholesterol oximes in mice increases transcription of cytoprotective genes and improves transcriptome alterations induced by alpha-synuclein overexpression in nigrostriatal dopaminergic neurons.</title><author><name sortKey="Richter, Franziska" sort="Richter, Franziska" uniqKey="Richter F" first="Franziska" last="Richter">Franziska Richter</name><affiliation><nlm:affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Gao, Fuying" sort="Gao, Fuying" uniqKey="Gao F" first="Fuying" last="Gao">Fuying Gao</name><affiliation><nlm:affiliation>Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Medvedeva, Vera" sort="Medvedeva, Vera" uniqKey="Medvedeva V" first="Vera" last="Medvedeva">Vera Medvedeva</name><affiliation><nlm:affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Lee, Patrick" sort="Lee, Patrick" uniqKey="Lee P" first="Patrick" last="Lee">Patrick Lee</name><affiliation><nlm:affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bove, Nicholas" sort="Bove, Nicholas" uniqKey="Bove N" first="Nicholas" last="Bove">Nicholas Bove</name><affiliation><nlm:affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Fleming, Sheila M" sort="Fleming, Sheila M" uniqKey="Fleming S" first="Sheila M" last="Fleming">Sheila M. Fleming</name><affiliation><nlm:affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Michaud, Magali" sort="Michaud, Magali" uniqKey="Michaud M" first="Magali" last="Michaud">Magali Michaud</name><affiliation><nlm:affiliation>Trophos S.A. Parc Scientifique de Luminy, Case 931, 13288 Marseille Cedex 9, France.</nlm:affiliation></affiliation></author><author><name sortKey="Lemesre, Vincent" sort="Lemesre, Vincent" uniqKey="Lemesre V" first="Vincent" last="Lemesre">Vincent Lemesre</name><affiliation><nlm:affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Patassini, Stefano" sort="Patassini, Stefano" uniqKey="Patassini S" first="Stefano" last="Patassini">Stefano Patassini</name><affiliation><nlm:affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</nlm:affiliation></affiliation></author><author><name sortKey="De La Rosa, Krystal" sort="De La Rosa, Krystal" uniqKey="De La Rosa K" first="Krystal" last="De La Rosa">Krystal De La Rosa</name><affiliation><nlm:affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Mulligan, Caitlin K" sort="Mulligan, Caitlin K" uniqKey="Mulligan C" first="Caitlin K" last="Mulligan">Caitlin K. Mulligan</name><affiliation><nlm:affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Sioshansi, Pedrom C" sort="Sioshansi, Pedrom C" uniqKey="Sioshansi P" first="Pedrom C" last="Sioshansi">Pedrom C. Sioshansi</name><affiliation><nlm:affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Zhu, Chunni" sort="Zhu, Chunni" uniqKey="Zhu C" first="Chunni" last="Zhu">Chunni Zhu</name><affiliation><nlm:affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Coppola, Giovanni" sort="Coppola, Giovanni" uniqKey="Coppola G" first="Giovanni" last="Coppola">Giovanni Coppola</name><affiliation><nlm:affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA; Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</nlm:affiliation></affiliation></author><author><name sortKey="Bordet, Thierry" sort="Bordet, Thierry" uniqKey="Bordet T" first="Thierry" last="Bordet">Thierry Bordet</name><affiliation><nlm:affiliation>Trophos S.A. Parc Scientifique de Luminy, Case 931, 13288 Marseille Cedex 9, France.</nlm:affiliation></affiliation></author><author><name sortKey="Pruss, Rebecca M" sort="Pruss, Rebecca M" uniqKey="Pruss R" first="Rebecca M" last="Pruss">Rebecca M. Pruss</name><affiliation><nlm:affiliation>Trophos S.A. Parc Scientifique de Luminy, Case 931, 13288 Marseille Cedex 9, France.</nlm:affiliation></affiliation></author><author><name sortKey="Chesselet, Marie Francoise" sort="Chesselet, Marie Francoise" uniqKey="Chesselet M" first="Marie-Françoise" last="Chesselet">Marie-Françoise Chesselet</name><affiliation><nlm:affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA. Electronic address: mchesselet@mednet.ucla.edu.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Neurobiology of disease</title><idno type="eISSN">1095-953X</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Brain (drug effects)</term><term>Brain (metabolism)</term><term>Cholestenones (pharmacokinetics)</term><term>Cholestenones (pharmacology)</term><term>Corpus Striatum (drug effects)</term><term>Corpus Striatum (metabolism)</term><term>Dopamine Agonists (pharmacology)</term><term>Dopaminergic Neurons (drug effects)</term><term>Dopaminergic Neurons (metabolism)</term><term>Gene Expression (drug effects)</term><term>Humans</term><term>Male</term><term>Mice, Transgenic</term><term>Movement Disorders (drug therapy)</term><term>Movement Disorders (metabolism)</term><term>Neuroprotective Agents (pharmacokinetics)</term><term>Neuroprotective Agents (pharmacology)</term><term>Oximes (pharmacokinetics)</term><term>Oximes (pharmacology)</term><term>Parkinsonian Disorders (drug therapy)</term><term>Parkinsonian Disorders (metabolism)</term><term>RNA, Messenger (metabolism)</term><term>Secosteroids (pharmacokinetics)</term><term>Secosteroids (pharmacology)</term><term>Substantia Nigra (drug effects)</term><term>Substantia Nigra (metabolism)</term><term>Transcriptome (drug effects)</term><term>alpha-Synuclein (genetics)</term><term>alpha-Synuclein (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>RNA, Messenger</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Cholestenones</term><term>Neuroprotective Agents</term><term>Oximes</term><term>Secosteroids</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Brain</term><term>Corpus Striatum</term><term>Dopaminergic Neurons</term><term>Gene Expression</term><term>Substantia Nigra</term><term>Transcriptome</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Movement Disorders</term><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term><term>Corpus Striatum</term><term>Dopaminergic Neurons</term><term>Movement Disorders</term><term>Parkinsonian Disorders</term><term>Substantia Nigra</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Cholestenones</term><term>Dopamine Agonists</term><term>Neuroprotective Agents</term><term>Oximes</term><term>Secosteroids</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term><term>Male</term><term>Mice, Transgenic</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Cholesterol-oximes TRO19622 and TRO40303 target outer mitochondrial membrane proteins and have beneficial effects in preclinical models of neurodegenerative diseases leading to their advancement to clinical trials. Dopaminergic neurons degenerate in Parkinson's disease (PD) and are prone to oxidative stress and mitochondrial dysfunction. In order to provide insights into the neuroprotective potential of TRO19622 and TRO40303 for dopaminergic neurons in vivo, we assessed their effects on gene expression in laser captured nigrostriatal dopaminergic neurons of wildtype mice and of mice that over-express alpha-synuclein, a protein involved in both familial and sporadic forms of PD (Thy1-aSyn mice). Young mice were fed the drugs in food pellets or a control diet from 1 to 4months of age, approximately 10months before the appearance of striatal dopamine loss in this model. Unbiased weighted gene co-expression network analysis (WGCNA) of transcriptional changes revealed effects of cholesterol oximes on transcripts related to mitochondria, cytoprotection and anti-oxidant response in wild-type and transgenic mice, including increased transcription of stress defense (e.g. Prdx1, Prdx2, Glrx2, Hspa9, Pink1, Drp1, Trak1) and dopamine-related (Th, Ddc, Gch1, Dat, Vmat2, Drd2, Chnr6a) genes. Even at this young age transgenic mice showed alterations in transcripts implicated in mitochondrial function and oxidative stress (e.g. Bcl-2, Bax, Casp3, Nos2), and both drugs normalized about 20% of these alterations. Young Thy1-aSyn mice exhibit motor deficits that differ from parkinsonism and are established before the onset of treatment; these deficits were not improved by cholesterol oximes. However, high doses of TRO40303 improved olfaction and produced the same effects as dopamine agonists on a challenging beam test, specifically an increase in footslips, an observation congruent with its effects on transcripts involved in dopamine synthesis. High doses of TRO19622 increased alpha-synuclein aggregates in the substantia nigra; this effect, not seen with TRO40303 was inconsistent and may represent a protective mechanism as in other neurodegenerative diseases. Overall, the results suggest that cholesterol oximes, while not improving early effects of alpha-synuclein overexpression on motor behavior or pathology, may ameliorate the function and resilience of dopaminergic neurons in vivo and support further studies of neuroprotection in models with dopaminergic cell loss.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24844147</PMID><DateCreated><Year>2014</Year><Month>07</Month><Day>14</Day></DateCreated><DateCompleted><Year>2015</Year><Month>03</Month><Day>12</Day></DateCompleted><DateRevised><Year>2016</Year><Month>10</Month><Day>25</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1095-953X</ISSN><JournalIssue CitedMedium="Internet"><Volume>69</Volume><PubDate><Year>2014</Year><Month>Sep</Month></PubDate></JournalIssue><Title>Neurobiology of disease</Title><ISOAbbreviation>Neurobiol. Dis.</ISOAbbreviation></Journal><ArticleTitle>Chronic administration of cholesterol oximes in mice increases transcription of cytoprotective genes and improves transcriptome alterations induced by alpha-synuclein overexpression in nigrostriatal dopaminergic neurons.</ArticleTitle><Pagination><MedlinePgn>263-75</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.nbd.2014.05.012</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0969-9961(14)00130-2</ELocationID><Abstract><AbstractText>Cholesterol-oximes TRO19622 and TRO40303 target outer mitochondrial membrane proteins and have beneficial effects in preclinical models of neurodegenerative diseases leading to their advancement to clinical trials. Dopaminergic neurons degenerate in Parkinson's disease (PD) and are prone to oxidative stress and mitochondrial dysfunction. In order to provide insights into the neuroprotective potential of TRO19622 and TRO40303 for dopaminergic neurons in vivo, we assessed their effects on gene expression in laser captured nigrostriatal dopaminergic neurons of wildtype mice and of mice that over-express alpha-synuclein, a protein involved in both familial and sporadic forms of PD (Thy1-aSyn mice). Young mice were fed the drugs in food pellets or a control diet from 1 to 4months of age, approximately 10months before the appearance of striatal dopamine loss in this model. Unbiased weighted gene co-expression network analysis (WGCNA) of transcriptional changes revealed effects of cholesterol oximes on transcripts related to mitochondria, cytoprotection and anti-oxidant response in wild-type and transgenic mice, including increased transcription of stress defense (e.g. Prdx1, Prdx2, Glrx2, Hspa9, Pink1, Drp1, Trak1) and dopamine-related (Th, Ddc, Gch1, Dat, Vmat2, Drd2, Chnr6a) genes. Even at this young age transgenic mice showed alterations in transcripts implicated in mitochondrial function and oxidative stress (e.g. Bcl-2, Bax, Casp3, Nos2), and both drugs normalized about 20% of these alterations. Young Thy1-aSyn mice exhibit motor deficits that differ from parkinsonism and are established before the onset of treatment; these deficits were not improved by cholesterol oximes. However, high doses of TRO40303 improved olfaction and produced the same effects as dopamine agonists on a challenging beam test, specifically an increase in footslips, an observation congruent with its effects on transcripts involved in dopamine synthesis. High doses of TRO19622 increased alpha-synuclein aggregates in the substantia nigra; this effect, not seen with TRO40303 was inconsistent and may represent a protective mechanism as in other neurodegenerative diseases. Overall, the results suggest that cholesterol oximes, while not improving early effects of alpha-synuclein overexpression on motor behavior or pathology, may ameliorate the function and resilience of dopaminergic neurons in vivo and support further studies of neuroprotection in models with dopaminergic cell loss.</AbstractText><CopyrightInformation>Copyright © 2014 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Richter</LastName><ForeName>Franziska</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gao</LastName><ForeName>Fuying</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Medvedeva</LastName><ForeName>Vera</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Patrick</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bove</LastName><ForeName>Nicholas</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fleming</LastName><ForeName>Sheila M</ForeName><Initials>SM</Initials><AffiliationInfo><Affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Michaud</LastName><ForeName>Magali</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Trophos S.A. Parc Scientifique de Luminy, Case 931, 13288 Marseille Cedex 9, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lemesre</LastName><ForeName>Vincent</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Patassini</LastName><ForeName>Stefano</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>De La Rosa</LastName><ForeName>Krystal</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mulligan</LastName><ForeName>Caitlin K</ForeName><Initials>CK</Initials><AffiliationInfo><Affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sioshansi</LastName><ForeName>Pedrom C</ForeName><Initials>PC</Initials><AffiliationInfo><Affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Chunni</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Coppola</LastName><ForeName>Giovanni</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA; Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bordet</LastName><ForeName>Thierry</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Trophos S.A. Parc Scientifique de Luminy, Case 931, 13288 Marseille Cedex 9, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pruss</LastName><ForeName>Rebecca M</ForeName><Initials>RM</Initials><AffiliationInfo><Affiliation>Trophos S.A. Parc Scientifique de Luminy, Case 931, 13288 Marseille Cedex 9, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chesselet</LastName><ForeName>Marie-Françoise</ForeName><Initials>MF</Initials><AffiliationInfo><Affiliation>Department of Neurology, The David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA. Electronic address: mchesselet@mednet.ucla.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>P30 NS062691</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P50 NS038367</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>05</Month><Day>18</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Neurobiol Dis</MedlineTA><NlmUniqueID>9500169</NlmUniqueID><ISSNLinking>0969-9961</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C549911">3,5-seco-4-norcholestan-5-one oxime-3-ol</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002783">Cholestenones</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018491">Dopamine Agonists</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D018696">Neuroprotective Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D010091">Oximes</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012333">RNA, Messenger</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C497604">SNCA protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D012632">Secosteroids</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051844">alpha-Synuclein</NameOfSubstance></Chemical><Chemical><RegistryNumber>A6778U5IFY</RegistryNumber><NameOfSubstance UI="C522838">olesoxime</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Cell Stem Cell. 2013 Jun 6;12(6):713-26</RefSource><PMID Version="1">23602540</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Neurotherapeutics. 2013 Jul;10(3):391-9</RefSource><PMID Version="1">23512373</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Prog Neurobiol. 2013 Jul-Aug;106-107:17-32</RefSource><PMID Version="1">23643800</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Exp Neurol. 2013 Sep;247:582-94</RefSource><PMID Version="1">23481547</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Mitochondrion. 2013 Nov;13(6):688-97</RefSource><PMID 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MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008822" MajorTopicYN="N">Mice, Transgenic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009069" MajorTopicYN="N">Movement Disorders</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018696" MajorTopicYN="N">Neuroprotective Agents</DescriptorName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010091" MajorTopicYN="N">Oximes</DescriptorName><QualifierName UI="Q000493" MajorTopicYN="N">pharmacokinetics</QualifierName><QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D020734" MajorTopicYN="N">Parkinsonian 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effects</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></MeshHeadingList><OtherID Source="NLM">NIHMS611930</OtherID><OtherID Source="NLM">PMC4135465</OtherID><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Alpha-synuclein</Keyword><Keyword MajorTopicYN="N">Laser capture microdissection</Keyword><Keyword MajorTopicYN="N">Mitochondrial function</Keyword><Keyword MajorTopicYN="N">Neuroprotection</Keyword><Keyword MajorTopicYN="N">Parkinson's disease</Keyword><Keyword MajorTopicYN="N">Transcriptome analysis</Keyword><Keyword MajorTopicYN="N">Transgenic mice</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>04</Month><Day>06</Day></PubMedPubDate><PubMedPubDate 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|texte= Chronic administration of cholesterol oximes in mice increases transcription of cytoprotective genes and improves transcriptome alterations induced by alpha-synuclein overexpression in nigrostriatal dopaminergic neurons.
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