2004
DOI: 10.1523/jneurosci.1233-04.2004
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Disrupted Spermine Homeostasis: A Novel Mechanism in Polyglutamine-Mediated Aggregation and Cell Death

Abstract: Our data suggest a novel mechanism whereby pathological-length polyglutamine (polyQ) proteins promote the spermine synthetic pathway, increasing polyQ-aggregation and cell death. As detected in a cell-free turbidity assay, spermine promotes aggregation of thio-polyQ62 in a dose-dependent manner.

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Cited by 19 publications
(24 citation statements)
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“…Utilizing an in vitro solubility assay, spermine was more effective than spermidine and putrescine in enhancing formation of insoluble aggregates (Colton et al 2004). These data may be relevant to the finding that spermine synthetic pathway was upregulated when an expanded polyQ protein was expressed in neuronal cells (Colton et al 2004). …”
Section: Modulation Of Protein Aggregation By Tg2 Aminylationmentioning
confidence: 83%
See 1 more Smart Citation
“…Utilizing an in vitro solubility assay, spermine was more effective than spermidine and putrescine in enhancing formation of insoluble aggregates (Colton et al 2004). These data may be relevant to the finding that spermine synthetic pathway was upregulated when an expanded polyQ protein was expressed in neuronal cells (Colton et al 2004). …”
Section: Modulation Of Protein Aggregation By Tg2 Aminylationmentioning
confidence: 83%
“…In addition, cells expressing expanded polyQ protein can modify polyamine synthesis offering new therapeutic approaches in the treatment of neurodegenerative diseases (Colton et al 2004;Colton et al 2006).…”
Section: Modulation Of Protein Aggregation By Tg2 Aminylationmentioning
confidence: 99%
“…82 Other groups using a non-neuronal cell model showed increased ARG1 expression, NOS, and arginase activity in HD mutant cells that correlated with an increase in arginine uptake. 83 Dysregulation of arginase by altered manganese homeostasis/bioavailability could result in localized ammonia and NOrelated toxic processes as well as altered production of glutamate and GABA, which require the conversion of ornithine from arginine as a precursor for their synthesis. 84 These HD phenotypes could be the result of altered bioavailability of manganese, as has been seen in manganese exposed mouse striatal cells and striatal tissues.…”
Section: Arginase a Manganese-dependent Enzymementioning
confidence: 99%
“…88 CATHa katekolaminerjik (CAD) hüc-relerinde mutant htt proteininin poliamin metabolizmasını olumsuz etkilediği ve artan in vitro poliamin miktarı ile mutant htt proteini agregat oluşumu arasında paralel bir bağlantı olduğu bilinmektedir. 89 Neonatal sıçanlarda poliamin biyosentezinin durdurulmasının, erişkinlik evresinde özellikle serebellumda nöronal kayıplara neden olduğu belirlenmiştir. 90,91 Poliaminlerin sinir sisteminde bu tip önemli bir etkide bulunmalarının temelinde NMDAR ile etkileşimleri olduğu düşünülmektedir.…”
Section: Eksi̇totoksi̇si̇tede Nmdar Nfκb Ve Poli̇ami̇n İli̇şki̇si̇unclassified
“…Bu çalışmalardan ilki, artan in vitro poliamin miktarı ile mutant htt agregatları oluşumunun paralellik gösterdiğini, ikincisi ise otopsi beyinlerinin putamen bölgesinde Spm miktarının azaldığını ortaya koymuştur. 88,89 Bu bulgular ışığında poliaminlerin, Huntington hastalığının patogenezine dahil oldukları söylenebilir. Ancak bu veriler, cevaplanması gereken birçok soruyu da beraberinde getirir.…”
Section: Sonuçunclassified