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Nutrients. 2016 Sep 9;8(9). pii: E556. doi: 10.3390/nu8090556.

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

Author information

1
Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China. tiantiantmu@126.com.
2
Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China. baidongtmu@126.com.
3
Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China. liwen828@163.com.
4
Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China. huangguowei@tmu.edu.cn.
5
Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin 300070, China. liuhuan@tmu.edu.cn.

Abstract

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.

KEYWORDS:

Alzheimer’s disease; Aβ generation; folic acid; microRNAs; secretase

PMID:
27618097
PMCID:
PMC5037541
DOI:
10.3390/nu8090556
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no conflict of interest.

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