Lysosome-dependent pathways as a unifying theme in Parkinson's disease.
Identifieur interne : 000D20 ( Main/Exploration ); précédent : 000D19; suivant : 000D21Lysosome-dependent pathways as a unifying theme in Parkinson's disease.
Auteurs : George K. Tofaris [Royaume-Uni]Source :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2012.
English descriptors
- KwdEn :
- Genetic Linkage, Humans, Lysosomes (genetics), Lysosomes (metabolism), Lysosomes (pathology), Mutation, Neurons (metabolism), Neurons (pathology), Parkinson Disease (genetics), Parkinson Disease (metabolism), Parkinson Disease (pathology), Signal Transduction (genetics), Signal Transduction (physiology), alpha-Synuclein (genetics), alpha-Synuclein (metabolism).
- MESH :
- chemical , genetics : alpha-Synuclein.
- genetics : Lysosomes, Parkinson Disease, Signal Transduction.
- metabolism : Lysosomes, Neurons, Parkinson Disease, alpha-Synuclein.
- pathology : Lysosomes, Neurons, Parkinson Disease.
- physiology : Signal Transduction.
- Genetic Linkage, Humans, Mutation.
Abstract
Although the pathogenesis of Parkinson's disease (PD) is considered multifactorial, evidence from genetics and cell biology has implicated specific molecular pathways. This article summarizes evidence that suggests that the level of intracellular alpha-synuclein is critical for the onset of neurodegeneration with Lewy bodies and dependent, to a large extent, on lysosomal degradation. The function of other key proteins that emerged from genetics is discussed: Pink1 and Parkin regulate the degradation of damaged mitochondria by the lysosome (mitophagy). Glucocerebrosidase and ATP13A2 are important components of this degradative organelle. VPS35 and LRRK2 may regulate trafficking within lysosome-dependent pathways, such as autophagy and endosomal vesicle recycling. Clinically, diffuse alpha-synucleinopathy or dementia seems to correlate with mutations which interfere with the broader function of lysosomal pathways, whereas a predominantly motor syndrome and nigrostriatal degeneration is associated with specific defects in mitophagy. Based on these studies, it is proposed that a protein network involved in trafficking to, or degradation by, lysosomes could be sufficient to explain the phenotypic spectrum within PD in a unifying biochemical pathway.
DOI: 10.1002/mds.25136
PubMed: 22927213
Affiliations:
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Le document en format XML
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Tofaris</name><affiliation wicri:level="4"><nlm:affiliation>Nuffield Department of Clinical Neurosciences and Oxford Parkinson's Disease Center, University of Oxford, Oxford, United Kingdom. george.tofaris@ndcn.ox.ac.uk</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Nuffield Department of Clinical Neurosciences and Oxford Parkinson's Disease Center, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2012">2012</date><idno type="doi">10.1002/mds.25136</idno><idno type="RBID">pubmed:22927213</idno><idno type="pmid">22927213</idno><idno type="wicri:Area/PubMed/Corpus">000C57</idno><idno type="wicri:Area/PubMed/Curation">000C57</idno><idno type="wicri:Area/PubMed/Checkpoint">000D49</idno><idno type="wicri:Area/Ncbi/Merge">003789</idno><idno type="wicri:Area/Ncbi/Curation">003789</idno><idno type="wicri:Area/Ncbi/Checkpoint">003789</idno><idno type="wicri:Area/Main/Merge">000D41</idno><idno type="wicri:Area/Main/Curation">000D20</idno><idno type="wicri:Area/Main/Exploration">000D20</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Lysosome-dependent pathways as a unifying theme in Parkinson's disease.</title><author><name sortKey="Tofaris, George K" sort="Tofaris, George K" uniqKey="Tofaris G" first="George K" last="Tofaris">George K. Tofaris</name><affiliation wicri:level="4"><nlm:affiliation>Nuffield Department of Clinical Neurosciences and Oxford Parkinson's Disease Center, University of Oxford, Oxford, United Kingdom. george.tofaris@ndcn.ox.ac.uk</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Nuffield Department of Clinical Neurosciences and Oxford Parkinson's Disease Center, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName><orgName type="university">Université d'Oxford</orgName></affiliation></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Genetic Linkage</term><term>Humans</term><term>Lysosomes (genetics)</term><term>Lysosomes (metabolism)</term><term>Lysosomes (pathology)</term><term>Mutation</term><term>Neurons (metabolism)</term><term>Neurons (pathology)</term><term>Parkinson Disease (genetics)</term><term>Parkinson Disease (metabolism)</term><term>Parkinson Disease (pathology)</term><term>Signal Transduction (genetics)</term><term>Signal Transduction (physiology)</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" qualifier="genetics" xml:lang="en"><term>Lysosomes</term><term>Parkinson Disease</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lysosomes</term><term>Neurons</term><term>Parkinson Disease</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lysosomes</term><term>Neurons</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Genetic Linkage</term><term>Humans</term><term>Mutation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Although the pathogenesis of Parkinson's disease (PD) is considered multifactorial, evidence from genetics and cell biology has implicated specific molecular pathways. This article summarizes evidence that suggests that the level of intracellular alpha-synuclein is critical for the onset of neurodegeneration with Lewy bodies and dependent, to a large extent, on lysosomal degradation. The function of other key proteins that emerged from genetics is discussed: Pink1 and Parkin regulate the degradation of damaged mitochondria by the lysosome (mitophagy). Glucocerebrosidase and ATP13A2 are important components of this degradative organelle. VPS35 and LRRK2 may regulate trafficking within lysosome-dependent pathways, such as autophagy and endosomal vesicle recycling. Clinically, diffuse alpha-synucleinopathy or dementia seems to correlate with mutations which interfere with the broader function of lysosomal pathways, whereas a predominantly motor syndrome and nigrostriatal degeneration is associated with specific defects in mitophagy. Based on these studies, it is proposed that a protein network involved in trafficking to, or degradation by, lysosomes could be sufficient to explain the phenotypic spectrum within PD in a unifying biochemical pathway.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Oxfordshire</li></region><settlement><li>Oxford</li></settlement><orgName><li>Université d'Oxford</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Tofaris, George K" sort="Tofaris, George K" uniqKey="Tofaris G" first="George K" last="Tofaris">George K. Tofaris</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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