Limits...
Effects of Folic Acid on Secretases Involved in A β Deposition in APP/PS1 Mice

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

Folate reduced hippocampal amyloid plaque loads in APP/PS1 (amyloid precursor protein)/(presenilin 1) mice. With bam-10 immunohistochemical staining following the administration, compared with the control group, the deposition of Aβ was significantly decreased in both 120 μg/kg and 600 μg/kg groups (A,B); scale bar = 100 μm. Enzyme-linked immuno sorbent assay (ELISA) was used to measure Aβ levels in brain tissues. Compared with the control group, folic acid administration decreased Aβ42 deposition, but not Aβ40 (C,D). The Aβ42 level was further decreased in the 600 μg/kg group compared to the 120 μg/kg group. After eight weeks, the folate deficiency diet reduced serum folate. Folic acid administration increased serum folate compared with the control group (E). The data were expressed as means ± SD values, n = 6 animals/group. a: p < 0.05 versus the Control group; b: p < 0.05 versus the 120 μg/kg group.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5037541&req=5

nutrients-08-00556-f001: Folate reduced hippocampal amyloid plaque loads in APP/PS1 (amyloid precursor protein)/(presenilin 1) mice. With bam-10 immunohistochemical staining following the administration, compared with the control group, the deposition of Aβ was significantly decreased in both 120 μg/kg and 600 μg/kg groups (A,B); scale bar = 100 μm. Enzyme-linked immuno sorbent assay (ELISA) was used to measure Aβ levels in brain tissues. Compared with the control group, folic acid administration decreased Aβ42 deposition, but not Aβ40 (C,D). The Aβ42 level was further decreased in the 600 μg/kg group compared to the 120 μg/kg group. After eight weeks, the folate deficiency diet reduced serum folate. Folic acid administration increased serum folate compared with the control group (E). The data were expressed as means ± SD values, n = 6 animals/group. a: p < 0.05 versus the Control group; b: p < 0.05 versus the 120 μg/kg group.

Mentions: Immunohistochemical analysis showed that the accumulated Aβ levels in brain tissue were higher in the deficiency group and lower in two folic acid supplementation groups than that in the control group (F[3,20] = 10.16, p < 0.05; Figure 1A,B).


Effects of Folic Acid on Secretases Involved in A β Deposition in APP/PS1 Mice
Folate reduced hippocampal amyloid plaque loads in APP/PS1 (amyloid precursor protein)/(presenilin 1) mice. With bam-10 immunohistochemical staining following the administration, compared with the control group, the deposition of Aβ was significantly decreased in both 120 μg/kg and 600 μg/kg groups (A,B); scale bar = 100 μm. Enzyme-linked immuno sorbent assay (ELISA) was used to measure Aβ levels in brain tissues. Compared with the control group, folic acid administration decreased Aβ42 deposition, but not Aβ40 (C,D). The Aβ42 level was further decreased in the 600 μg/kg group compared to the 120 μg/kg group. After eight weeks, the folate deficiency diet reduced serum folate. Folic acid administration increased serum folate compared with the control group (E). The data were expressed as means ± SD values, n = 6 animals/group. a: p < 0.05 versus the Control group; b: p < 0.05 versus the 120 μg/kg group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037541&req=5

nutrients-08-00556-f001: Folate reduced hippocampal amyloid plaque loads in APP/PS1 (amyloid precursor protein)/(presenilin 1) mice. With bam-10 immunohistochemical staining following the administration, compared with the control group, the deposition of Aβ was significantly decreased in both 120 μg/kg and 600 μg/kg groups (A,B); scale bar = 100 μm. Enzyme-linked immuno sorbent assay (ELISA) was used to measure Aβ levels in brain tissues. Compared with the control group, folic acid administration decreased Aβ42 deposition, but not Aβ40 (C,D). The Aβ42 level was further decreased in the 600 μg/kg group compared to the 120 μg/kg group. After eight weeks, the folate deficiency diet reduced serum folate. Folic acid administration increased serum folate compared with the control group (E). The data were expressed as means ± SD values, n = 6 animals/group. a: p < 0.05 versus the Control group; b: p < 0.05 versus the 120 μg/kg group.
Mentions: Immunohistochemical analysis showed that the accumulated Aβ levels in brain tissue were higher in the deficiency group and lower in two folic acid supplementation groups than that in the control group (F[3,20] = 10.16, p < 0.05; Figure 1A,B).

View Article: PubMed Central - PubMed

ABSTRACT

Alzheimer&rsquo;s disease (AD) is the most common type of dementia. Amyloid-&beta; protein (A&beta;) is identified as the core protein of neuritic plaques. A&beta; is generated by the sequential cleavage of the amyloid precursor protein (APP) via the APP cleaving enzyme (&alpha;-secretase, or &beta;-secretase) and &gamma;-secretase. Previous studies indicated that folate deficiency elevated A&beta; 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 A&beta; by regulating &alpha;-, &beta;-, and &gamma;-secretase. Herein, we demonstrated that folic acid reduced the deposition of A&beta;42 in APP/PS1 mice brain by decreasing the mRNA and protein expressions of &beta;-secretase [beta-site APP-cleaving enzyme 1 (BACE1)] and &gamma;-secretase complex catalytic component&mdash;presenilin 1 (PS1)&mdash;in APP/PS1 mice brain. Meanwhile, folic acid increased the levels of ADAM9 and ADAM10, which are important &alpha;-secretases in ADAM (a disintegrin and metalloprotease) family. However, folic acid has no impact on the protein expression of nicastrin (Nct), another component of &gamma;-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 A&beta; deposition may relate to making APP metabolism through non-amyloidogenic pathway by decreasing &beta;-secretase and increasing &alpha;-secretase. MicroRNA (miRNA) may involve in the regulation mechanism of folic acid on secretase expression.

No MeSH data available.


Related in: MedlinePlus