A Novel Perspective for Alzheimer's Disease: Vitamin D Receptor Suppression by Amyloid-β and Preventing the Amyloid-β Induced Alterations by Vitamin D in Cortical Neurons

Amyloid-beta (A beta) is the core component of amyloid plaques of Alzheimer's disease (AD). The effects of A beta include damage to neuronal plasma membrane, disruption of Ca2+ homeostasis, and alterations of neurotrophic factor levels. The aim of this study was to determine the effects of A beta treatment on vitamin D receptor (VDR), L-type voltage sensitive calcium channels A1C (LVSCC A1C), NGF, and observing the effects of vitamin D treatment on A beta induced alterations in primary cortical neurons. As to the latter, we aimed to test the suggested neuroprotective role of vitamin D as a neglected neurosteroid. The expressions of VDR and LVSCC A1C were studied with qRT-PCR and Western blotting. NGF and cytotoxicity levels were determined by ELISA. Apoptotic cell death was investigated with caspase-3 protein expression by Western blotting. Our results showed that the A beta triggers neurodegeneration not only by inducing LVSCC A1C expression and NGF levels and but also by dramatically suppressing VDR expression. Administration of vitamin D to this model protected neurons by preventing cytotoxicity and apoptosis, and also by downregulating LVSCC A1C and upregulating VDR. Additionally, vitamin D brought NGF expression to a state of equilibrium and did not show its apoptosis inducing effects. Consequently, prevention of A beta toxicity which was one of the major component of AD type pathology by vitamin D treatment and understanding how A beta effects vitamin D related pathways, might open up new frontiers in clarifying molecular mechanisms of neurodegeneration and provide basis for novel perspectives in both preventing and treating AD.