The protective effect of curcumin on Aβ induced aberrant cell cycle reentry on primary cultured rat cortical neurons

Abstract

Objectives: Alzheimer's disease (AD) is a neurodegenerative disorder marked by progressive loss of memory and impairment of cognitive ability. One current hypothesis for AD pathogenesis is that neuronal death is linked to aberrant cell-cycle re-entry. In AD, neurons have been shown to enter the cell cycle inappropriately without the ability to complete it fully and the aberrant re-entry leads to its death. Curcumin has been reported as having a neural protective effect on the AD model, and could modulate the proliferation of tumor cells through the regulation of cyclin D1 and c-myc cell signaling pathways. In this study, we first observed the protective action of curcumin on Abeta-induced neuron damage, and then investigated whether this protective effect was a result of the inhibition of cell cycle advance.

Materials and methods: We used MTT assay and TUNEL assay to observe the effect of curcumin on Abeta-induced neuron death, and then examined the activated caspase-3 protein level to further confirm the protective effect of curcumin against Abeta-induced neuron toxicity. Next, we further investigate whether the inhibition of cell cycle reentry was mediated by the therapeutic effect of curcumin on Abeta induced primary cultured neuron damage by Brdu label assay and western blot assay.

Results: The results showed that administration of curcumin (1-10 microM) could inhibit Abeta25-35 (40 microg/ml) induced primary cultured rat cortical neuron death, down-regulating activated caspase-3 protein expression. Furthermore, treatment with curcumin could inhibit abnormal activated cyclin D1 protein level, and decrease the Brdu positive cells in proportion to the Abeta25-35 treatment neurons.

Conclusions: All the results suggest that curcumin has a protective effect against Abeta-induced toxicity in cultured rat cortical neurons, the inhibition of cell cycle re-entry at least partly mediating the therapeutic effect of curcumin in the AD model in vitro.