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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

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Abstract

Alpha-linolenic acid (ALA), which is an omega-3 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 (Aβ)-mediated neurotoxicity, neuronal apoptosis and amyloid precursor protein (APP) processing are unclear. To investigate the neuroprotective effect of ALA, we treated Aβ25-35-induced SH-SY5Y cells with ALA (1, 2.5, 5 and 25 μg/mL). In our results, Aβ25-35-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 Aβ25-35 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 Aβ25-35 cause an increase in protein expression of APP-C-terminal fragment β, β-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 α-secretase activity by up-regulating the protein levels of A distintegrin and metalloprotease 10 and tumor necrosis factor-α-converting enzyme, indicating that ALA could promote non-amyloidogenic signaling pathways. ALA also significantly attenuated Aβ25-35-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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Acknowledgment

This work was carried out with the support of the “Cooperative Research Program for Agriculture Science & Technology Development (PJ01015603),” Rural Development Administration, Republic of Korea.

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Authors and Affiliations

  1. Department of Food Science and Nutrition and Kimchi Research Institute, Pusan National University, Busan, 46241, Republic of Korea

    Ah Young Lee & Eun Ju Cho

  2. Department of Southern Area Crop Science, National Institute of Crop Science, Rural Development Administration, Miryang, 50424, Republic of Korea

    Myoung-Hee Lee

  3. Department of Integrative Plant Science, Chung-Ang University, Anseong, 17546, Republic of Korea

    Sanghyun Lee

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  1. Ah Young Lee
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Correspondence to Sanghyun Lee or Eun Ju Cho.

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Lee, A.Y., Lee, MH., Lee, S. et al. 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. Appl Biol Chem 61, 61–71 (2018). https://doi.org/10.1007/s13765-017-0334-4

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