Zingerone activates VMAT2 during MPP+‐induced Cell Death

Abstract

Parkinson's disease (PD) is characterized by a progressive and selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and striatum. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is used to produce an animal model for PD, and it is converted to 1-methyl-4-phenylpyridine (MPP(+)) in animals. MPP(+) accumulation leads to neuronal cell death. Vesicular monoamine transporter 2 (VMAT2) regulates the accumulation of monoamine neurotransmitters into synaptic vesicles and is involved in neuroprotection against neurotoxin-induced cell death. Recently, zingerone has been reported to reduce oxidative stress and inhibit inflammation. Therefore, we examined the effect of zingerone on neuronal cell death in a PD model. In an MPP(+) and MPTP-mediated PD model, neuronal cell survival was increased by zingerone without modifying neuroinflammation or reactive oxygen species generation. Zingerone also induced ERK activation and VMAT2 expression, leading to the attenuation of MPP(+)-induced neuronal cell death. Our current results suggest that zingerone has a neuroprotective effect in a PD model.