What genetics tells us about the causes and mechanisms of Parkinson's disease.
Identifieur interne : 000946 ( PubMed/Corpus ); précédent : 000945; suivant : 000947What genetics tells us about the causes and mechanisms of Parkinson's disease.
Auteurs : Olga Corti ; Suzanne Lesage ; Alexis BriceSource :
- Physiological reviews [ 1522-1210 ] ; 2011.
English descriptors
- KwdEn :
- Animals, Disease Models, Animal, Genetic Predisposition to Disease (genetics), Humans, Intracellular Signaling Peptides and Proteins (genetics), Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Mutation (genetics), Oncogene Proteins (genetics), Parkinson Disease (genetics), Protein Deglycase DJ-1, Protein Kinases (genetics), Protein-Serine-Threonine Kinases (genetics), Ubiquitin-Protein Ligases (genetics).
- MESH :
- chemical , genetics : Intracellular Signaling Peptides and Proteins, Oncogene Proteins, Protein Kinases, Protein-Serine-Threonine Kinases, Ubiquitin-Protein Ligases.
- genetics : Genetic Predisposition to Disease, Mutation, Parkinson Disease.
- Animals, Disease Models, Animal, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Protein Deglycase DJ-1.
Abstract
Parkinson's disease (PD) is a common motor disorder of mysterious etiology. It is due to the progressive degeneration of the dopaminergic neurons of the substantia nigra and is accompanied by the appearance of intraneuronal inclusions enriched in α-synuclein, the Lewy bodies. It is becoming increasingly clear that genetic factors contribute to its complex pathogenesis. Over the past decade, the genetic basis of rare PD forms with Mendelian inheritance, representing no more than 10% of the cases, has been investigated. More than 16 loci and 11 associated genes have been identified so far; genome-wide association studies have provided convincing evidence that polymorphic variants in these genes contribute to sporadic PD. The knowledge acquired of the functions of their protein products has revealed pathways of neurodegeneration that may be shared between inherited and sporadic PD. An impressive set of data in different model systems strongly suggest that mitochondrial dysfunction plays a central role in clinically similar, early-onset autosomal recessive PD forms caused by parkin and PINK1, and possibly DJ-1 gene mutations. In contrast, α-synuclein accumulation in Lewy bodies defines a spectrum of disorders ranging from typical late-onset PD to PD dementia and including sporadic and autosomal dominant PD forms due to mutations in SCNA and LRRK2. However, the pathological role of Lewy bodies remains uncertain, as they may or may not be present in PD forms with one and the same LRRK2 mutation. Impairment of autophagy-based protein/organelle degradation pathways is emerging as a possible unifying but still fragile pathogenic scenario in PD. Strengthening these discoveries and finding other convergence points by identifying new genes responsible for Mendelian forms of PD and exploring their functions and relationships are the main challenges of the next decade. It is also the way to follow to open new promising avenues of neuroprotective treatment for this devastating disorder.
DOI: 10.1152/physrev.00022.2010
PubMed: 22013209
Links to Exploration step
pubmed:22013209Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">What genetics tells us about the causes and mechanisms of Parkinson's disease.</title><author><name sortKey="Corti, Olga" sort="Corti, Olga" uniqKey="Corti O" first="Olga" last="Corti">Olga Corti</name><affiliation><nlm:affiliation>Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière; Institut National de la Santé et de la Recherche Médicale U.975, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2011">2011</date><idno type="RBID">pubmed:22013209</idno><idno type="pmid">22013209</idno><idno type="doi">10.1152/physrev.00022.2010</idno><idno type="wicri:Area/PubMed/Corpus">000946</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000946</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">What genetics tells us about the causes and mechanisms of Parkinson's disease.</title><author><name sortKey="Corti, Olga" sort="Corti, Olga" uniqKey="Corti O" first="Olga" last="Corti">Olga Corti</name><affiliation><nlm:affiliation>Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière; Institut National de la Santé et de la Recherche Médicale U.975, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Lesage, Suzanne" sort="Lesage, Suzanne" uniqKey="Lesage S" first="Suzanne" last="Lesage">Suzanne Lesage</name></author><author><name sortKey="Brice, Alexis" sort="Brice, Alexis" uniqKey="Brice A" first="Alexis" last="Brice">Alexis Brice</name></author></analytic><series><title level="j">Physiological reviews</title><idno type="eISSN">1522-1210</idno><imprint><date when="2011" type="published">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Genetic Predisposition to Disease (genetics)</term><term>Humans</term><term>Intracellular Signaling Peptides and Proteins (genetics)</term><term>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</term><term>Mutation (genetics)</term><term>Oncogene Proteins (genetics)</term><term>Parkinson Disease (genetics)</term><term>Protein Deglycase DJ-1</term><term>Protein Kinases (genetics)</term><term>Protein-Serine-Threonine Kinases (genetics)</term><term>Ubiquitin-Protein Ligases (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Intracellular Signaling Peptides and Proteins</term><term>Oncogene Proteins</term><term>Protein Kinases</term><term>Protein-Serine-Threonine Kinases</term><term>Ubiquitin-Protein Ligases</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Genetic Predisposition to Disease</term><term>Mutation</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Humans</term><term>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</term><term>Protein Deglycase DJ-1</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkinson's disease (PD) is a common motor disorder of mysterious etiology. It is due to the progressive degeneration of the dopaminergic neurons of the substantia nigra and is accompanied by the appearance of intraneuronal inclusions enriched in α-synuclein, the Lewy bodies. It is becoming increasingly clear that genetic factors contribute to its complex pathogenesis. Over the past decade, the genetic basis of rare PD forms with Mendelian inheritance, representing no more than 10% of the cases, has been investigated. More than 16 loci and 11 associated genes have been identified so far; genome-wide association studies have provided convincing evidence that polymorphic variants in these genes contribute to sporadic PD. The knowledge acquired of the functions of their protein products has revealed pathways of neurodegeneration that may be shared between inherited and sporadic PD. An impressive set of data in different model systems strongly suggest that mitochondrial dysfunction plays a central role in clinically similar, early-onset autosomal recessive PD forms caused by parkin and PINK1, and possibly DJ-1 gene mutations. In contrast, α-synuclein accumulation in Lewy bodies defines a spectrum of disorders ranging from typical late-onset PD to PD dementia and including sporadic and autosomal dominant PD forms due to mutations in SCNA and LRRK2. However, the pathological role of Lewy bodies remains uncertain, as they may or may not be present in PD forms with one and the same LRRK2 mutation. Impairment of autophagy-based protein/organelle degradation pathways is emerging as a possible unifying but still fragile pathogenic scenario in PD. Strengthening these discoveries and finding other convergence points by identifying new genes responsible for Mendelian forms of PD and exploring their functions and relationships are the main challenges of the next decade. It is also the way to follow to open new promising avenues of neuroprotective treatment for this devastating disorder.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">22013209</PMID><DateCreated><Year>2011</Year><Month>10</Month><Day>20</Day></DateCreated><DateCompleted><Year>2011</Year><Month>12</Month><Day>13</Day></DateCompleted><DateRevised><Year>2016</Year><Month>11</Month><Day>25</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1522-1210</ISSN><JournalIssue CitedMedium="Internet"><Volume>91</Volume><Issue>4</Issue><PubDate><Year>2011</Year><Month>Oct</Month></PubDate></JournalIssue><Title>Physiological reviews</Title><ISOAbbreviation>Physiol. 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More than 16 loci and 11 associated genes have been identified so far; genome-wide association studies have provided convincing evidence that polymorphic variants in these genes contribute to sporadic PD. The knowledge acquired of the functions of their protein products has revealed pathways of neurodegeneration that may be shared between inherited and sporadic PD. An impressive set of data in different model systems strongly suggest that mitochondrial dysfunction plays a central role in clinically similar, early-onset autosomal recessive PD forms caused by parkin and PINK1, and possibly DJ-1 gene mutations. In contrast, α-synuclein accumulation in Lewy bodies defines a spectrum of disorders ranging from typical late-onset PD to PD dementia and including sporadic and autosomal dominant PD forms due to mutations in SCNA and LRRK2. However, the pathological role of Lewy bodies remains uncertain, as they may or may not be present in PD forms with one and the same LRRK2 mutation. Impairment of autophagy-based protein/organelle degradation pathways is emerging as a possible unifying but still fragile pathogenic scenario in PD. Strengthening these discoveries and finding other convergence points by identifying new genes responsible for Mendelian forms of PD and exploring their functions and relationships are the main challenges of the next decade. 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