Abstract:
:In a forward genetic screen in Drosophila melanogaster, aimed to identify genes required for normal locomotor function, we isolated dPPCS (the second enzyme of the Coenzyme A biosynthesis pathway). The entire Drosophila CoA synthesis route was dissected, annotated and additional CoA mutants were obtained (dPANK/fumble) or generated (dPPAT-DPCK). Drosophila CoA mutants suffer from neurodegeneration, altered lipid homeostasis and the larval brains display increased apoptosis. Also, de novo CoA biosynthesis is required to maintain DNA integrity during the development of the central nervous system. In humans, mutations in the PANK2 gene, the first enzyme in the CoA synthesis route, are associated with pantothenate kinase-associated neurodegeneration. Currently, the pathogenesis of this neurodegenerative disease is poorly understood. We provide the first comprehensive analysis of the physiological implications of mutations in the entire CoA biosynthesis route in an animal model system. Surprisingly, our findings reveal a major role of this conserved pathway in maintaining DNA and cellular integrity, explaining how impaired CoA synthesis during CNS development can elicit a neurodegenerative phenotype.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Bosveld F,Rana A,van der Wouden PE,Lemstra W,Ritsema M,Kampinga HH,Sibon OCdoi
10.1093/hmg/ddn105subject
Has Abstractpub_date
2008-07-01 00:00:00pages
2058-69issue
13eissn
0964-6906issn
1460-2083pii
ddn105journal_volume
17pub_type
杂志文章abstract::Glomerular disease is one of the most common causes of end-stage renal failure. Increasing evidence suggests that these glomerulopathies are frequently caused by primary lesions in the renal podocytes. One of the major consequences of podocyte lesions is the accumulation of mesangial matrix in the glomerular basement ...
journal_title:Human molecular genetics
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更新日期:2013-12-01 00:00:00
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doi:10.1093/hmg/10.23.2727
更新日期:2001-11-01 00:00:00
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pub_type: 更正并重新发布的文章,杂志文章,评审
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