1 research outputs found
Vitamin D Receptor Regulates Amyloid Beta 1–42 Production with Protein Disulfide Isomerase A3
The
challenge of understanding the biology of neuronal amyloid
processing could provide a basis for understanding the amyloid pathology
in Alzheimer’s disease (AD). Based on our previous studies,
we have suggested that AD might be the consequence of a hormonal imbalance
in which the critical hormone is vitamin D. The present study primarily
focused on the creation of a condition that prevents the genomic or
nongenomic action of vitamin D by disrupting vitamin D receptors (VDR
or PDIA3/1,25MARRS); the effects of these disruptions on the series
of proteins involved in secretases that play a crucial role in amyloid
pathology and on amyloid beta (Aβ) production in primary cortical
neurons were observed. VDR and PDIA3/1,25MARRS genes were silenced
separately or simultaneously in E16 primary rat cortical neurons.
The expression of target genes involved in APP processing, including
Presenilin1, Presenilin2, Nicastrin, BACE1, ADAM10, and APP, was investigated
with qRT-PCR and Western blot in this model. 1,25-Dihydroxyvitamin
D<sub>3</sub> treatments were used to verify any transcriptional regulation
data gathered from siRNA treatments by determining the mRNA expression
of the target genes. Immunofluorescence labeling was used for the
verification of silencing experiments and intracellular Aβ1–42
production. Extracellular Aβ1–42 level was assessed with
ELISA. mRNA and protein expression results showed that 1,25-dihydroxyvitamin
D<sub>3</sub> might affect the transcriptional regulation of the genes
involved in APP processing. The intracellular and extracellular Aβ1–42
measurements in our study support this suggestion. Consequently, we
suggest that 1,25-dihydroxyvitamin D<sub>3</sub> and its receptors
are important parts of the amyloid processing pathway in neurons