The Cast of Molecular Characters in Parkinson's Disease
Identifieur interne : 001701 ( Main/Exploration ); précédent : 001700; suivant : 001702The Cast of Molecular Characters in Parkinson's Disease
Auteurs : Kah Leong Lim ; Valina L. Dawson [États-Unis] ; Ted M. Dawson [États-Unis]Source :
- Annals of the New York Academy of SciencesPARKINSON'S DISEASE: The Life Cycle of the Dopamine Neuron [ 0077-8923 ] ; 2003-06.
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Abstract
Abstract: Parkinson's Disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopamine neurons and the accumulation of Lewy bodies and neurites. Recent advances indicate that PD is due in some individuals to genetic mutations in α‐synuclein, parkin, and ubiquitin C‐terminal hydrolase L1 (UCHL1). All three PD‐linked gene products are related directly or indirectly to the functioning of the cellular ubiquitin proteasomal system (UPS), suggesting that UPS dysfunction may be important in PD pathogenesis. Indeed, emerging evidence indicates that derangements of the UPS may be one of the underlying mechanisms of PD pathogenesis. The function of parkin as an ubiquitin protein ligase positions it as an important player in both familial and idiopathic PD. We recently demonstrated that parkin mediates a nondegradative form of ubiquitination on synphilin‐1 that could contribute to synphilin‐1's aggregation in PD. Our results implicate parkin involvement in the formation of Lewy bodies associated with sporadic PD. This review discusses the role of the UPS, as well as the modus operandi of the three PD candidate felons (α‐synuclein, parkin, and UCHL1) along with their conspirators in bringing about dopaminergic cell death in PD.
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DOI: 10.1111/j.1749-6632.2003.tb07465.x
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Dawson</name><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287</wicri:regionArea><wicri:noRegion>Maryland 21287</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287</wicri:regionArea><wicri:noRegion>Maryland 21287</wicri:noRegion></affiliation><affiliation wicri:level="1"><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287</wicri:regionArea><wicri:noRegion>Maryland 21287</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of the New York Academy of SciencesPARKINSON'S DISEASE: The Life Cycle of the Dopamine Neuron</title><idno type="ISSN">0077-8923</idno><idno type="eISSN">1749-6632</idno><imprint><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2003-06">2003-06</date><biblScope unit="volume">991</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="80">80</biblScope><biblScope unit="page" to="92">92</biblScope></imprint><idno type="ISSN">0077-8923</idno></series><idno type="istex">178BBD878FE4A1A4E036E25B6805E0924A46334B</idno><idno type="DOI">10.1111/j.1749-6632.2003.tb07465.x</idno><idno type="ArticleID">NYAS80</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0077-8923</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson's disease</term><term>UCHL1</term><term>parkin</term><term>ubiquitination</term><term>ubiquitin‐proteasome system</term><term>α‐synuclein</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Parkinson's Disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopamine neurons and the accumulation of Lewy bodies and neurites. Recent advances indicate that PD is due in some individuals to genetic mutations in α‐synuclein, parkin, and ubiquitin C‐terminal hydrolase L1 (UCHL1). All three PD‐linked gene products are related directly or indirectly to the functioning of the cellular ubiquitin proteasomal system (UPS), suggesting that UPS dysfunction may be important in PD pathogenesis. Indeed, emerging evidence indicates that derangements of the UPS may be one of the underlying mechanisms of PD pathogenesis. The function of parkin as an ubiquitin protein ligase positions it as an important player in both familial and idiopathic PD. We recently demonstrated that parkin mediates a nondegradative form of ubiquitination on synphilin‐1 that could contribute to synphilin‐1's aggregation in PD. Our results implicate parkin involvement in the formation of Lewy bodies associated with sporadic PD. This review discusses the role of the UPS, as well as the modus operandi of the three PD candidate felons (α‐synuclein, parkin, and UCHL1) along with their conspirators in bringing about dopaminergic cell death in PD.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Lim, Kah Leong" sort="Lim, Kah Leong" uniqKey="Lim K" first="Kah Leong" last="Lim">Kah Leong Lim</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Dawson, Valina L" sort="Dawson, Valina L" uniqKey="Dawson V" first="Valina L." last="Dawson">Valina L. Dawson</name></noRegion><name sortKey="Dawson, Ted M" sort="Dawson, Ted M" uniqKey="Dawson T" first="Ted M." last="Dawson">Ted M. Dawson</name><name sortKey="Dawson, Ted M" sort="Dawson, Ted M" uniqKey="Dawson T" first="Ted M." last="Dawson">Ted M. Dawson</name><name sortKey="Dawson, Ted M" sort="Dawson, Ted M" uniqKey="Dawson T" first="Ted M." last="Dawson">Ted M. Dawson</name><name sortKey="Dawson, Valina L" sort="Dawson, Valina L" uniqKey="Dawson V" first="Valina L." last="Dawson">Valina L. Dawson</name><name sortKey="Dawson, Valina L" sort="Dawson, Valina L" uniqKey="Dawson V" first="Valina L." last="Dawson">Valina L. Dawson</name><name sortKey="Dawson, Valina L" sort="Dawson, Valina L" uniqKey="Dawson V" first="Valina L." last="Dawson">Valina L. Dawson</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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