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2009 | 69 | 1 |
Tytuł artykułu

Inhibition of 12-lipoxygenase protects against amyloid beta peptides-evoked toxicity, memory impairment and alteration of locomotor activity

Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
The pro-infl ammatory enzyme 12/15-lipoxygenase (12/15-LOX) is upregulated in Alzheimerís disease (AD), but the role of the enzyme in a amyloid beta (AB)-evoked toxicity is not fully understood. Its pro-oxidative activity may contribute to the pathophysiology of AD. The aim of this study was to analyze the expression and activity of 12-LOX in animal model of AD. The role of 12-LOX in AB42-evoked memory impairment and locomotory activity and the effect of systemic infl ammation on AB-dependent alterations were also studied. Then the relationship between AB concentration and 12-LOX was examined using PC12 cells transfected with human wild-type and mutant AB precursor protein (APP) gene. Twelve-month-old C57Bl6 mice were injected with AB42 (1 nmol, icv) alone or simultaneously with lipopolysaccharide (LPS; 1 mg/kg, ip). Some mice received 12-LOX inhibitor, beicalein (10 mg/kg, ip). Our results indicated that AB signifi cantly increased 12-LOX expression and activity in hippocampus. Beicalein effectively prevented AB-induced 12-LOX activation and protected mice against memory defi cit and locomotory disturbances. In vitro studies demonstrated the signifi cant relationship between AB level and 12-LOX expression, oxidative stress and NF-κB activation. Beicalein protected PC12 cells against NF-κB nuclear translocation. Our data indicated that 12-LOX is involved in AB toxicity. Beicalein protected mice against memory defi cit and locomotory disturbances, suggesting that 12/15-LOX inhibitors may provide new therapeutic opportunities in treatment of AD. Supported by MS&HE scientifi c network 28/E-32/SN-0053/2007
Słowa kluczowe
Wydawca
-
Rocznik
Tom
69
Numer
1
Opis fizyczny
p.87
Twórcy
autor
  • Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
autor
  • Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland
  • Department of Cellular Signalling, Mossakowski Medical Research, Centre Polish Academy of Sciences, Warsaw, Poland
Bibliografia
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.agro-a7d1475b-6a8c-4fd2-a695-6512cedc8020
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