[Possible effect of N-Acetyl-L-cysteine on Aβ(25-35)-induced tau hyperphosphorylation].

Objective To investigate the possible effect and mechanism of N-Acetyl-L-cysteine (NAC) on fibrillar Aβ(25-35)-induced tau hyperphosphorylation. Methods The phosphorylation of tau was induced by Aβ(25-35) in primary cortical neuron. Neurons were incubated in the absent or present Aβ(25-35), or pre-incubated NAC then co-incubated in Aβ. The measurement of ROS was performed on a microplate fluorometer. The proteins of p35/p25, cdk5, pT205 and pS404 were detected by Western blot. Results In Aβ treated group, the ROS, pT205 and pS404 level were obviously higher than that in non-treated with Aβ group for 12 h (t=-6.35, P<0.05; t=-5, P<0.05; t=-4.57, P<0.05). However, in neurons pre-incubated with (10 mmol/L) NAC and then co-incubated with 20 μmol/L Aβ, the ROS, pT205 and pS404 level were significantly decreased compared with that of Aβ group (t=3.47, P<0.05; t=3.88, P<0.05 and t=3.64, P<0.05); Upon Aβ exposure for 12 h, cortical neurons showed a statistically significant increase in p25 when compared to the control group (t=-6.20, P<0.05). However, pre-treatment with NAC showed a decrease in p25 as compared to neurons treated with Aβ alone for 12 h (t=4.72, P<0.05). Conclusion NAC attenuated the Aβ(25-35)-induced tau hyperphosphorylation through CDK5 pathway. Key words: N-acetylcysteine (NAC); Amyloid beta peptides; Cyclin-dependent kinase 5; tau; Phosphorylation