The pattern of neuronal loss and survival may reflect differential expression of proteasome activators in Parkinson's disease
Identifieur interne : 000514 ( Main/Exploration ); précédent : 000513; suivant : 000515The pattern of neuronal loss and survival may reflect differential expression of proteasome activators in Parkinson's disease
Auteurs : Kevin St. P. Mcnaught [États-Unis] ; Ruth Jnobaptiste [États-Unis] ; Tehone Jackson [États-Unis] ; Toni-Ann Jengelley [États-Unis]Source :
- Synapse [ 0887-4476 ] ; 2010-03.
English descriptors
- KwdEn :
Abstract
The basis of neuronal vulnerability, degeneration, and sparing in PD are unknown, but there is increasing evidence to suggest that the ubiquitin‐proteasome system (UPS) plays an important role in the pathogenesis of the disorder. In this study, we employed an immunocytochemical approach to determine if the differential expression of key UPS components in various brain regions and cells might underlie the pattern of neuronal degeneration and survival seen in PD. We showed that the ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2), and 26/20S proteasome α‐ and β‐subunits, are abundantly expressed in the substantia nigra pars compacta (SNc) and in cultured dopaminergic neurons. Although the proteasome activator PA700 is expressed in the medial SNc, levels are low in the lateral region, and expression of the other proteasome activator, PA28, is near absent in the entire SNc. PA28 (but not PA700) was found to be poorly expressed in noradrenergic neurons in the locus coeruleus (LC) compared with adjacent cells in the mesencephalic nucleus. PA700 and PA28 are also poorly expressed in dopaminergic neurons compared with other cell types in culture. Inhibition of proteasomal function, generation of misfolded proteins, induction of oxidative stress or impairment of mitochondrial complex I activity, caused a compensatory upregulation in PA700 and PA28 in a variety of cells but not in dopaminergic neurons in culture. These findings are consistent with the demonstration that, in sporadic PD, proteasomal activity and levels of PA700/PA28 are reduced in the SNc butare markedly upregulated in regions/cells that are spared from the neurodegenerative process. Thus, the differential distribution and activity of proteasome activations could play a significant role in the pathogenesis of PD. Synapse 64:241–250, 2010. © 2009 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/syn.20719
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">The pattern of neuronal loss and survival may reflect differential expression of proteasome activators in Parkinson's disease</title><author><name sortKey="Mcnaught, Kevin St P" sort="Mcnaught, Kevin St P" uniqKey="Mcnaught K" first="Kevin St. P." last="Mcnaught">Kevin St. P. Mcnaught</name></author><author><name sortKey="Jnobaptiste, Ruth" sort="Jnobaptiste, Ruth" uniqKey="Jnobaptiste R" first="Ruth" last="Jnobaptiste">Ruth Jnobaptiste</name></author><author><name sortKey="Jackson, Tehone" sort="Jackson, Tehone" uniqKey="Jackson T" first="Tehone" last="Jackson">Tehone Jackson</name></author><author><name sortKey="Jengelley, Toni Nn" sort="Jengelley, Toni Nn" uniqKey="Jengelley T" first="Toni-Ann" last="Jengelley">Toni-Ann Jengelley</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:1A5C176990746FB27A0814A34DFA85A11113CA76</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1002/syn.20719</idno><idno type="url">https://api.istex.fr/document/1A5C176990746FB27A0814A34DFA85A11113CA76/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002B68</idno><idno type="wicri:Area/Main/Curation">002802</idno><idno type="wicri:Area/Main/Exploration">000514</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">The pattern of neuronal loss and survival may reflect differential expression of proteasome activators in Parkinson's disease</title><author><name sortKey="Mcnaught, Kevin St P" sort="Mcnaught, Kevin St P" uniqKey="Mcnaught K" first="Kevin St. P." last="Mcnaught">Kevin St. P. Mcnaught</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Neurology, Mount Sinai School of Medicine, New York</wicri:cityArea></affiliation></author><author><name sortKey="Jnobaptiste, Ruth" sort="Jnobaptiste, Ruth" uniqKey="Jnobaptiste R" first="Ruth" last="Jnobaptiste">Ruth Jnobaptiste</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Neurology, Mount Sinai School of Medicine, New York</wicri:cityArea></affiliation></author><author><name sortKey="Jackson, Tehone" sort="Jackson, Tehone" uniqKey="Jackson T" first="Tehone" last="Jackson">Tehone Jackson</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Neurology, Mount Sinai School of Medicine, New York</wicri:cityArea></affiliation></author><author><name sortKey="Jengelley, Toni Nn" sort="Jengelley, Toni Nn" uniqKey="Jengelley T" first="Toni-Ann" last="Jengelley">Toni-Ann Jengelley</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Neurology, Mount Sinai School of Medicine, New York</wicri:cityArea></affiliation></author></analytic><monogr></monogr><series><title level="j">Synapse</title><title level="j" type="abbrev">Synapse</title><idno type="ISSN">0887-4476</idno><idno type="eISSN">1098-2396</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-03">2010-03</date><biblScope unit="volume">64</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="241">241</biblScope><biblScope unit="page" to="250">250</biblScope></imprint><idno type="ISSN">0887-4476</idno></series><idno type="istex">1A5C176990746FB27A0814A34DFA85A11113CA76</idno><idno type="DOI">10.1002/syn.20719</idno><idno type="ArticleID">SYN20719</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0887-4476</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>PA700 and PA28</term><term>Parkinson's disease</term><term>dopaminergic neurons</term><term>substantia nigra pars compacta</term><term>ubiquitin‐proteasome system</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The basis of neuronal vulnerability, degeneration, and sparing in PD are unknown, but there is increasing evidence to suggest that the ubiquitin‐proteasome system (UPS) plays an important role in the pathogenesis of the disorder. In this study, we employed an immunocytochemical approach to determine if the differential expression of key UPS components in various brain regions and cells might underlie the pattern of neuronal degeneration and survival seen in PD. We showed that the ubiquitin activating enzyme (E1), ubiquitin conjugating enzyme (E2), and 26/20S proteasome α‐ and β‐subunits, are abundantly expressed in the substantia nigra pars compacta (SNc) and in cultured dopaminergic neurons. Although the proteasome activator PA700 is expressed in the medial SNc, levels are low in the lateral region, and expression of the other proteasome activator, PA28, is near absent in the entire SNc. PA28 (but not PA700) was found to be poorly expressed in noradrenergic neurons in the locus coeruleus (LC) compared with adjacent cells in the mesencephalic nucleus. PA700 and PA28 are also poorly expressed in dopaminergic neurons compared with other cell types in culture. Inhibition of proteasomal function, generation of misfolded proteins, induction of oxidative stress or impairment of mitochondrial complex I activity, caused a compensatory upregulation in PA700 and PA28 in a variety of cells but not in dopaminergic neurons in culture. These findings are consistent with the demonstration that, in sporadic PD, proteasomal activity and levels of PA700/PA28 are reduced in the SNc butare markedly upregulated in regions/cells that are spared from the neurodegenerative process. Thus, the differential distribution and activity of proteasome activations could play a significant role in the pathogenesis of PD. Synapse 64:241–250, 2010. © 2009 Wiley‐Liss, Inc.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>État de New York</li></region></list><tree><country name="États-Unis"><region name="État de New York"><name sortKey="Mcnaught, Kevin St P" sort="Mcnaught, Kevin St P" uniqKey="Mcnaught K" first="Kevin St. P." last="Mcnaught">Kevin St. P. Mcnaught</name></region><name sortKey="Jackson, Tehone" sort="Jackson, Tehone" uniqKey="Jackson T" first="Tehone" last="Jackson">Tehone Jackson</name><name sortKey="Jengelley, Toni Nn" sort="Jengelley, Toni Nn" uniqKey="Jengelley T" first="Toni-Ann" last="Jengelley">Toni-Ann Jengelley</name><name sortKey="Jnobaptiste, Ruth" sort="Jnobaptiste, Ruth" uniqKey="Jnobaptiste R" first="Ruth" last="Jnobaptiste">Ruth Jnobaptiste</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000514 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000514 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Sante
|area= ParkinsonV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= ISTEX:1A5C176990746FB27A0814A34DFA85A11113CA76
|texte= The pattern of neuronal loss and survival may reflect differential expression of proteasome activators in Parkinson's disease
}}
| This area was generated with Dilib version V0.6.23. |  |