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Effects of Folic Acid on Secretases Involved in Aβ Deposition in APP/PS1 Mice

Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China
Author to whom correspondence should be addressed.
Nutrients 2016, 8(9), 556;
Received: 30 June 2016 / Revised: 31 August 2016 / Accepted: 6 September 2016 / Published: 9 September 2016
Alzheimer’s disease (AD) is the most common type of dementia. Amyloid-β protein (Aβ) is identified as the core protein of neuritic plaques. Aβ is generated by the sequential cleavage of the amyloid precursor protein (APP) via the APP cleaving enzyme (α-secretase, or β-secretase) and γ-secretase. Previous studies indicated that folate deficiency elevated Aβ deposition in APP/PS1 mice, and this rise was prevented by folic acid. In the present study, we aimed to investigate whether folic acid could influence the generation of Aβ by regulating α-, β-, and γ-secretase. Herein, we demonstrated that folic acid reduced the deposition of Aβ42 in APP/PS1 mice brain by decreasing the mRNA and protein expressions of β-secretase [beta-site APP-cleaving enzyme 1 (BACE1)] and γ-secretase complex catalytic component—presenilin 1 (PS1)—in APP/PS1 mice brain. Meanwhile, folic acid increased the levels of ADAM9 and ADAM10, which are important α-secretases in ADAM (a disintegrin and metalloprotease) family. However, folic acid has no impact on the protein expression of nicastrin (Nct), another component of γ-secretase complex. Moreover, folic acid regulated the expression of miR-126-3p and miR-339-5p, which target ADAM9 and BACE1, respectively. Taken together, the effect of folic acid on Aβ deposition may relate to making APP metabolism through non-amyloidogenic pathway by decreasing β-secretase and increasing α-secretase. MicroRNA (miRNA) may involve in the regulation mechanism of folic acid on secretase expression. View Full-Text
Keywords: Alzheimer’s disease; folic acid; Aβ generation; secretase; microRNAs Alzheimer’s disease; folic acid; Aβ generation; secretase; microRNAs
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Tian, T.; Bai, D.; Li, W.; Huang, G.-W.; Liu, H. Effects of Folic Acid on Secretases Involved in Aβ Deposition in APP/PS1 Mice. Nutrients 2016, 8, 556.

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