Overexpression of an inactive mutant cathepsin D increases endogenous alpha-synuclein and cathepsin B activity in SH-SY5Y cells*
Identifieur interne : 001235 ( Ncbi/Checkpoint ); précédent : 001234; suivant : 001236Overexpression of an inactive mutant cathepsin D increases endogenous alpha-synuclein and cathepsin B activity in SH-SY5Y cells*
Auteurs : Donna Crabtree ; Matthew Dodson ; Xiaosen Ouyang ; Michaël Boyer-Guittaut [France] ; Qiuli Liang ; Mary E. Ballestas ; Naomi Fineberg ; Jianhua ZhangSource :
- Journal of neurochemistry [ 0022-3042 ] ; 2013.
Abstract
Parkinson’s disease (PD) is a neurodegenerative movement disorder. The histopathology of PD comprises proteinaceous inclusions known as
Url:
DOI: 10.1111/jnc.12497
PubMed: 24138030
PubMed Central: 3951679
Affiliations:
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PMC:3951679Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Overexpression of an inactive mutant cathepsin D increases endogenous alpha-synuclein and cathepsin B activity in SH-SY5Y cells<sup>*</sup>
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<wicri:noCountry code="subfield">University of Alabama at Birmingham</wicri:noCountry>
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<wicri:noCountry code="subfield">University of Alabama at Birmingham</wicri:noCountry>
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<affiliation><nlm:aff id="A2">Center for Free Radical Biology, University of Alabama at Birmingham</nlm:aff>
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<wicri:noCountry code="subfield">UAB School of Public Health</wicri:noCountry>
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<author><name sortKey="Fineberg, Naomi" sort="Fineberg, Naomi" uniqKey="Fineberg N" first="Naomi" last="Fineberg">Naomi Fineberg</name>
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<wicri:noCountry code="subfield">UAB School of Public Health</wicri:noCountry>
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<author><name sortKey="Zhang, Jianhua" sort="Zhang, Jianhua" uniqKey="Zhang J" first="Jianhua" last="Zhang">Jianhua Zhang</name>
<affiliation><nlm:aff id="A1">Department of Pathology, University of Alabama at Birmingham</nlm:aff>
<wicri:noCountry code="subfield">University of Alabama at Birmingham</wicri:noCountry>
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<series><title level="j">Journal of neurochemistry</title>
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<front><div type="abstract" xml:lang="en"><p id="P1">Parkinson’s disease (PD) is a neurodegenerative movement disorder. The histopathology of PD comprises proteinaceous inclusions known as <italic>Lewy bodies,</italic>
which contains aggregated α-synuclein. Cathepsin D (CD) is a lysosomal protease previously demonstrated to cleave α-synuclein and decrease its toxicity in both cell lines and mouse brains <italic>in vivo.</italic>
Here we show that pharmacological inhibition of CD, or introduction of catalytically inactive mutant CD resulted in decreased CD activity and increased cathepsin B activity, suggesting a possible compensatory response to inhibition of CD activity. However, this increased cathepsin B activity was not sufficient to maintain α-synuclein degradation, as evidenced by the accumulation of endogenous α-synuclein. Interestingly, the levels of LC3, LAMP1 and LAMP2, proteins involved in autophagy-lysosomal activities, as well as total lysosomal mass as assessed by LysoTracker flow cytometry, were unchanged. Neither autophagic flux nor proteasomal activities differ between cells over expressing wildtype versus mutant CD. These observations point to a critical regulatory role for that endogenous CD activity in dopaminergic cells in α-synuclein homeostasis which cannot be compensated for by increased Cathepsin B. These data support the potential need to enhance CD function in order to attenuate α-synuclein accumulation as a therapeutic strategy against development of synucleinopathy.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>France</li>
</country>
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<li>Franche-Comté</li>
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<tree><noCountry><name sortKey="Ballestas, Mary E" sort="Ballestas, Mary E" uniqKey="Ballestas M" first="Mary E." last="Ballestas">Mary E. Ballestas</name>
<name sortKey="Crabtree, Donna" sort="Crabtree, Donna" uniqKey="Crabtree D" first="Donna" last="Crabtree">Donna Crabtree</name>
<name sortKey="Dodson, Matthew" sort="Dodson, Matthew" uniqKey="Dodson M" first="Matthew" last="Dodson">Matthew Dodson</name>
<name sortKey="Fineberg, Naomi" sort="Fineberg, Naomi" uniqKey="Fineberg N" first="Naomi" last="Fineberg">Naomi Fineberg</name>
<name sortKey="Liang, Qiuli" sort="Liang, Qiuli" uniqKey="Liang Q" first="Qiuli" last="Liang">Qiuli Liang</name>
<name sortKey="Ouyang, Xiaosen" sort="Ouyang, Xiaosen" uniqKey="Ouyang X" first="Xiaosen" last="Ouyang">Xiaosen Ouyang</name>
<name sortKey="Zhang, Jianhua" sort="Zhang, Jianhua" uniqKey="Zhang J" first="Jianhua" last="Zhang">Jianhua Zhang</name>
</noCountry>
<country name="France"><region name="Bourgogne-Franche-Comté"><name sortKey="Boyer Guittaut, Michael" sort="Boyer Guittaut, Michael" uniqKey="Boyer Guittaut M" first="Michaël" last="Boyer-Guittaut">Michaël Boyer-Guittaut</name>
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