Edited by Jesus AvilaKeywords: Cdk5 Gsk-3b Amyloid beta Phosphorylation Alzheimer's disease a b s t r a c tThe aim of the present study was to analyse the alterations of Cyclin dependent kinase 5 (Cdk5) expression and phosphorylation in PC12 cells overexpressing Amyloid precursor protein (APP). Our results demonstrated enhanced cell death and increased levels of mRNA for the Cdk5 gene in APP-transfected cells. Significantly decreased phosphorylation of Cdk5 at Tyr15 was observed in APPsw cells, which is responsible for a reduction in Cdk5 activity. Cdk5-dependent phosphorylation of Glycogen synthase kinase-3b (Gsk-3b) at Ser9 was also decreased, which can lead to the increase of Gsk-3b activity and hyperphosphorylation of MAP tau. Our results demonstrate for the first time, a deregulation of Cdk5 phosphorylation in APP-transfected cells.

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Parkinson's disease is a slowly progressing disease, due to a lesion of dopaminergic neurons in the substantia nigra and a dramatic loss of dopamine in the striatum. It is now accepted that several environmental agents including the herbicide paraquat (PQ) may contribute to its pathogenesis. However, till now nothing is known about the role of glycogen synthase kinase-3β (GSK-3β) in the PQ toxicity. Therefore, the aim of this study was to examine the influence of 37-week administration of PQ in rats on the immunohistochemically measured levels of the total GSK-3β and its active, tyrosine 216 (pY216)-phosphorylated form in subcellular fractions of the midbrain with pons, as well as of the striatum. The present results revealed that the long-term PQ administration increased the levels of total and active forms of GSK-3β in the midbrain with pons, whereas decreased them in the striatum. Examination of the lesion extent showed a decrease in the number of tyrosine-immunoreactive neurons in the substantia nigra pars compacta, ventral tegmental area, and locus coeruleus, as well as lower DOPAC/dopamine ratio and noradrenaline level in the striatum in rats treated with PQ. The long-term PQ administration disturbed also motor activity of rats. Summarizing, the present data indicate that the long-term exposure of rats to PQ, a commonly used herbicide, diversely alters levels of GSK-3β in different brain structures, which may be associated with their vulnerability to its toxicity.

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