The role of Cdk5/p35 and cPLA2/LOX in neuroinflammation and neurodegeneration

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

Abstrakty

EN

Cyclin dependent kinase 5 (Cdk5) is implicated in the pathomechanism of Alzheimer’s disease (AD), as a kinase responsible for hyperphosphorylation of tau protein and aberrant metabolism of Amyloid β (Aβ) precursor protein. The previous data indicated the involvement of Cdk5 in regulation of cytosolic phospholipase A2 (cPLA2) gene, but its precise function is not fully understood. In our studies, we analyzed in animal AD model the role of Cdk5 in neuroinflammation and in regulation of cPLA2/lipoxygenase (LOX) pathway. Our data indicated an increase in gene expression for cPLA2, 5-LOX and 12/15-LOX in the hippocampus during the systemic inflammation. In parallel, we observed an increase in expression of the Cdk5 activating protein – Cdk5r1 (p35), suggesting the enhancement of Cdk5 activity and its possible role, as the regulatory factor. Using mouse AD model we demonstrated enhancement of 12-LOX expression and activity and cognitive impairment, which was prevented by 12-LOX inhibitor. Our results demonstrated the important role of inflammatory reaction in cognitive impairment. The relationship between Cdk5 and cPLA2/ LOX during neuroinflammation may have a significant implication for the pathomechanism of AD, and presents Cdk5/p35 as the promising target for improvement of AD therapy. This study was funded by grant from The National Science Centre 2011/03/B/NZ3/04549.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: Suppl.1
• Opis fizyczny: p.52

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