Abstract

Background: Oligomers of amyloid β (Aβ) in the brain correlate with synapse loss and dementia. The fungicide maneb (MB) and mancozeb (MZ) have been shown to activate the transcription factor NF-κB. Activation of NF-κB signaling pathway could initiate the transcription of β-amyloid precursor protein (AβPP) leading to increase Aβ level. Studies showed the cells treated with Aβ42 have the elevated level of phosphorylated double-stranded RNA dependent protein kinase (PKR) which is found to deteriorate the neurons in AD brains.
Objective: To reveal the effects of MB and MZ on AβPP and Aβ42 expressions and to elucidate the role of PKR in response to MB and MZ.
Methods: Western blot analysis and ELISA assay were conducted to investigate the expressions of AβPP and Aβ42 in PC12 cells treated with MB and MZ. The activation of PKR was determined by western blotting the level of phosphorylated PKR at Thr446 in SH-SY5Y cells treated with MB and MZ.
Results: MB and MZ increased AβPP and Aβ42 expressions in a dose-dependent manner. MB and MZ transiently activated PKR.
Conclusion: Studies showed that MB and MZ enhance parkinsonian toxin MPP+ cytotoxicity and trigger DNA damage. The results from this study further revealed that MB and MZ are associated with the increase of AβPP and Aβ42 expressions and elucidated that the PKR signaling pathway involves in MB and MZ induced cytotoxicity. This study provides the evidence about the relationship between fungicides and neurodegenerative diseases.

Keywords: Maneb; Mancozeb; AβPP; Aβ42; PKR