The role of quercetin on the survival of neuron-like PC12 cells and the expression of α-synuclein

Both genetic and environmental factors are important in the pathogenesis of Parkinson's disease. As alpha-synuclein is a major constituent of Lewy bodies, a pathologic hallmark of Parkinson's disease, genetic aspects of alpha-synuclein is widely studied. However, the influence of dietary factors such as quercetin on alpha-synuclein was rarely studied. Herein we aimed to study the neuroprotective role of quercetin against various toxins affecting apoptosis, autophagy and aggresome, and the role of quercetin on alpha-synuclein expression. PC12 cells were pre-treated with quercetin (100, 500, 1,000 mu M) and then together with various drugs such as 1-methyl-4-phenylpyridinium (MPP+; a free radical generator), 6-hydroxydopamine (6-OHDA; a free radical generator), ammonium chloride (an autophagy inhibitor), and nocodazole (an aggresome inhibitor). Cell viability was determined using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltertazolium bromide (MTT) assay. Apoptosis was detected by annexin V-fluorescein isothiocyanate and propidium iodide through the use of fluorescence activated cell sorter. alpha-Synuclein expression was detected by western blot assay and immunohistochemistry. The role of alpha-synuclein was further studied by knocking out alpha-synuclein using RNA interference. Cell viability increased at lower concentrations (100 and 500 mu M) of quercetin but decreased at higher concentration (1,000 mu M). Quercetin exerted neuroprotective effect against MPP+, ammonium chloride and nocodazole at 100 mu M. MPP+ induced apoptosis was decreased by 100 mu M quercetin. Quercetin treatment increased alpha-synuclein expression. However, knocking out alpha-synuclein exerted no significant effect on cell survival. In conclusion, quercetin is neuroprotective against toxic agents via affecting various mechanisms such as apoptosis, autophagy and aggresome. Because alpha-synuclein expression is increased by quercetin, the role of quercetin as an environmental factor in Parkinson's disease pathogenesis needs further investigation.