Metabolism in HD - Still a relevant mechanism?
Identifieur interne : 000521 ( Main/Exploration ); précédent : 000520; suivant : 000522Metabolism in HD - Still a relevant mechanism?
Auteurs : Wenzhen Duan [États-Unis] ; Mali Jiang [États-Unis] ; Jing Jin [États-Unis]Source :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2014.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Nerve Tissue Proteins, Peptides.
- chemical , metabolism : Adenosine Triphosphate.
- complications : Huntington Disease.
- etiology : Metabolic Diseases.
- genetics : Energy Metabolism, Huntington Disease, Metabolic Diseases.
- Humans.
Abstract
The polyglutamine expansion within huntingtin is the causative factor in the pathogenesis of Huntington’s disease (HD). Although the underlying mechanisms by which mutant huntingtin causes neuronal dysfunction and degeneration have not been fully elucidated, the compelling evidence suggests that mitochondrial dysfunction and compromised energy metabolism are key players in HD pathogenesis. Longitudinal studies of HD subjects have shown that reductions in glucose utilization before the disease clinical onset. Preferential striatal neurodegeneration, a hallmark of HD pathogenesis, has also been associated with interrupted energy metabolism. Data from genetic HD models indicate that mutant huntingtin disrupts mitochondrial bioenergetics and prevents ATP generation, implying altered energy metabolism as an important component of HD pathogenesis. Here we revisit the evidence of abnormal energy metabolism in the central nervous system of HD patients, overview our current understanding of the molecular mechanisms underlying abnormal metabolism induced by mutant huntingtin, and discuss the promising therapeutic development by halting abnormal metabolism in HD.
Url:
DOI: 10.1002/mds.25992
PubMed: 25124273
PubMed Central: 4163071
Affiliations:
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Still a relevant mechanism?</title><author><name sortKey="Duan, Wenzhen" sort="Duan, Wenzhen" uniqKey="Duan W" first="Wenzhen" last="Duan">Wenzhen Duan</name><affiliation wicri:level="2"><nlm:aff id="A1">Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation><affiliation wicri:level="2"><nlm:aff id="A3">Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Jiang, Mali" sort="Jiang, Mali" uniqKey="Jiang M" first="Mali" last="Jiang">Mali Jiang</name><affiliation wicri:level="2"><nlm:aff id="A1">Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Jin, Jing" sort="Jin, Jing" uniqKey="Jin J" first="Jing" last="Jin">Jing Jin</name><affiliation wicri:level="2"><nlm:aff id="A1">Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore</wicri:cityArea></affiliation></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenosine Triphosphate (metabolism)</term><term>Energy Metabolism (genetics)</term><term>Humans</term><term>Huntington Disease (complications)</term><term>Huntington Disease (genetics)</term><term>Metabolic Diseases (etiology)</term><term>Metabolic Diseases (genetics)</term><term>Nerve Tissue Proteins (genetics)</term><term>Peptides (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Nerve Tissue Proteins</term><term>Peptides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Adenosine Triphosphate</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Huntington Disease</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Metabolic Diseases</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Energy Metabolism</term><term>Huntington Disease</term><term>Metabolic Diseases</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Humans</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">The polyglutamine expansion within huntingtin is the causative factor in the pathogenesis of Huntington’s disease (HD). Although the underlying mechanisms by which mutant huntingtin causes neuronal dysfunction and degeneration have not been fully elucidated, the compelling evidence suggests that mitochondrial dysfunction and compromised energy metabolism are key players in HD pathogenesis. Longitudinal studies of HD subjects have shown that reductions in glucose utilization before the disease clinical onset. Preferential striatal neurodegeneration, a hallmark of HD pathogenesis, has also been associated with interrupted energy metabolism. Data from genetic HD models indicate that mutant huntingtin disrupts mitochondrial bioenergetics and prevents ATP generation, implying altered energy metabolism as an important component of HD pathogenesis. Here we revisit the evidence of abnormal energy metabolism in the central nervous system of HD patients, overview our current understanding of the molecular mechanisms underlying abnormal metabolism induced by mutant huntingtin, and discuss the promising therapeutic development by halting abnormal metabolism in HD.</p></div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Maryland</li></region></list><tree><country name="États-Unis"><region name="Maryland"><name sortKey="Duan, Wenzhen" sort="Duan, Wenzhen" uniqKey="Duan W" first="Wenzhen" last="Duan">Wenzhen Duan</name></region><name sortKey="Duan, Wenzhen" sort="Duan, Wenzhen" uniqKey="Duan W" first="Wenzhen" last="Duan">Wenzhen Duan</name><name sortKey="Duan, Wenzhen" sort="Duan, Wenzhen" uniqKey="Duan W" first="Wenzhen" last="Duan">Wenzhen Duan</name><name sortKey="Jiang, Mali" sort="Jiang, Mali" uniqKey="Jiang M" first="Mali" last="Jiang">Mali Jiang</name><name sortKey="Jin, Jing" sort="Jin, Jing" uniqKey="Jin J" first="Jing" last="Jin">Jing Jin</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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