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 α-synuclein is a major constituent of Lewy bodies, a pathologic hallmark of Parkinson's disease, genetic aspects of α-synuclein is widely studied. However, the influence of dietary factors such as quercetin on α-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 α-synuclein expression. PC12 cells were pre-treated with quercetin (100, 500, 1,000 μM) 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. α-Synuclein expression was detected by western blot assay and immunohistochemistry. The role of α-synuclein was further studied by knocking out α-synuclein using RNA interference. Cell viability increased at lower concentrations (100 and 500 μM) of quercetin but decreased at higher concentration (1,000 μM). Quercetin exerted neuroprotective effect against MPP(+), ammonium chloride and nocodazole at 100 μM. MPP(+) induced apoptosis was decreased by 100 μM quercetin. Quercetin treatment increased α-synuclein expression. However, knocking out α-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 α-synuclein expression is increased by quercetin, the role of quercetin as an environmental factor in Parkinson's disease pathogenesis needs further investigation.