Evidence indicates that
Parkinson's disease (PD), in addition to having a genetic aetiology, has an environmental component that contributes to disease onset and progression. The exact nature of any environmental agent contributing to PD is unknown in most cases. Given its similarity to
paraquat, an
agrochemical removed from registration in the EU for its suspected potential to cause PD, we have investigated the in vitro capacity of the related
herbicide Diquat to cause PD-like cell death.
Diquat showed greater toxicity towards SH-SY5Y
neuroblastoma cells and human midbrain neural cells than
paraquat and also
MPTP, which was independent of
dopamine transporter-mediated uptake.
Diquat caused cell death independently of
caspase activation, potentially via RIP1
kinase, with only a minor contribution from apoptosis, which was accompanied by enhanced
reactive oxygen species production in the absence of major inhibition of complex I of the mitochondrial respiratory chain. No changes in α-
synuclein expression were observed following 24-h or 4-week exposure.
Diquat may, therefore, kill neural tissue by programmed
necrosis rather than apoptosis, reflecting the pathological changes seen following high-level exposure, although its ability to promote PD is unclear.