Alpha-linolenic acid regulates amyloid precursor protein processing by mitogen-activated protein kinase pathway and neuronal apoptosis in amyloid beta-induced SH-SY5Y neuronal cells
2018
Lee, A.Y., Pusan National University, Busan, Republic of Korea | Lee, M.H., National Institute of Crop Science, Rural Development Administration, Miryang, Republic of Korea | Lee, S., Chung-Ang University, Anseong, Republic of Korea | Cho, E.J., Pusan National University, Busan, Republic of Korea
Alpha-linolenic acid (ALA), which is an omega3 fatty acid from plant oils, has been reported to have beneficial effects on human brain health. However, the protective effect of ALA and its mechanism of action against amyloid beta (Ab)-mediated neurotoxicity, neuronal apoptosis and amyloid precursor protein (APP) processing are unclear. To investigate the neuroprotective effect of ALA, we treated Ab25-35-induced SH-SY5Y cells with ALA (1, 2.5, 5 and 25 lg/mL). In our results, Ab25-35- induced neuronal cell loss was observed, whereas ALA significantly increased the cell viability and decreased lactate dehydrogenase release. In addition, over-production of reactive oxygen species caused by Ab25-35 was attenuated by treatment with ALA, and these inhibitory activities were mediated by regulation of the mitogen-activated protein kinase signaling pathway. Furthermore, our data shows that Ab25-35 cause an increase in protein expression of APP-C-terminal fragment b, b-site APP-cleaving enzyme and presenilin-1 in SH-SY5Y cells, while ALA significantly down-regulated the expression of those amyloidogenic APP processing-related proteins. In addition, we confirmed that ALA enhanced a-secretase activity by upregulating the protein levels of A distintegrin and metalloprotease 10 and tumor necrosis factor-a-converting enzyme, indicating that ALA could promote non-amyloidogenic signaling pathways. ALA also significantly attenuated Ab25-35-induced neuronal apoptosis by up-regulation of the Bcl-2/Bax ratio. These findings suggest that ALA may be a beneficial agent for promoting prevention of Alzheimer's disease.
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