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

• Autorzy: Czapski G.A. , Cakala M. , Strosznajder J.B.
• 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

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.87

Twórcy

autor

Czapski G.A.

• Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Cakala M.

• Department of Cellular Signalling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Strosznajder J.B.

• Department of Cellular Signalling, Mossakowski Medical Research, Centre Polish Academy of Sciences, Warsaw, Poland