Table 1.
Effects of vitamin D in experimental models of Alzheimer disease—in vitro studies.
| AD Model | Vitamin D Administration | Effects | References |
|---|---|---|---|
| Aβ(1–42) peptide-induced toxicity in differentiated SH-SY5Y cells | calcitriol (100 nM)/24 h prior to Aβ(1−42) peptide (1 μM)/6 h | ↑ cell viability ↑ sphingosine-1-phosphate, sphingosine kinase ↓ p38MAPK/ATF4 axis |
[97] |
| Aβ(25–35) peptide induced toxicity in SH-SY5Y cells | calcitriol (0.1 or 10 nM)/24 h after Aβ(25–35) peptide | ↑ cell viability ↑ VDR protein expression ↑ GDNF expression ↓ cell apoptosis ↓ ROS level ↓ p-tau/tau ↑ p-Akt/Akt |
[98] |
| Aβ(1–42) peptide-induced toxicity in primary cortical neuronal cultures | vitamin D3 (1 nM), curcumin (5 μM), vitamin D3 + curcumin Aβ(1–42) (1 µM)/72 h |
↓ lipid peroxidation ↑ reduced GSH ↑ GST enzyme level ↑ NGF |
[99] |
| SH-SY5Y cells | calcitriol (10–500 nM)/48 h | ↑ IL-34 mRNA and protein ↑ VDR expression |
[109] |
| SH-SY5Y wt cells, SH-SY5Y APP695 cells and N2a cells | calcifediol, maxacalcitol, calcipotriol, alfacalcidol, paricalcitol, doxercalciferol (100 nM)/24 h |
↓ Aβ-production ↑ Aβ-degradation ↓ γ-secretase activity ↓ β-secretase 1 ↓ IL-1β |
[113] |
| Aβ(25–35)-induced damage of BV-2 microglia cells | ergocalciferol (1 μM)/1 h prior to Aβ(25–35) (20 μM)/24 h | ↓ ROS, IL-6, IL-1β, TNF-α, iNOS, COX-2 and NF-κB activation | [110] |
| BBB model (bEnd.3 cells) HepG2 |
calcitriol (1–100 nM)/control or hypoxia/60 h/+ Aβ(1–40) (100 nM) calcitriol (1–100 nM)/6 h/ + Aβ(1–40) (115 nM) |
↓ cerebral Aβ1–40 level ↑ LRP-1 expression ↑ VDR expression ↓ RAGE expression ↑ Aβ1–40 uptake |
[59] |
| Hydrogen peroxide-induced damage of HUVEC line | vitamin D and VDR ligand (ZK191784) + hydrogen peroxide (200 μM)/20 min | ↓ apoptosis-related gene expression, ↑ pro-autophagic Beclin 1 and the phosphorylation of ERK1/2 and Akt, ↑ mitochondrial potential ↓ cytochrome C release and caspase activation |
[122] |
| NO-deprived BMECs | - | ↑ APP, BACE1, Aβ(1–41) and Aβ(1–42) peptides | [120] |
AD—Alzheimer’s Disease; Aβ—amyloid-beta peptide; Akt—protein kinase B; APP—amyloid precursor protein; ATF4—activating-transcription-factor-4; BACE1—amyloid precursor protein cleaving enzyme-1; BBB—Blood–Brain Barrier; bEnd.3—mouse brain microvascular endothelial cells line; BMECs—human brain microvascular endothelium; COX-2—cyclooxygenase-2; ERK—extracellular-signal-regulated kinase; GDNF—glial-cell-line-derived neurotrophic factor; GSH—gluthatione; GST—Glutathione S-transferase; HepG2—human hepatoblastoma cell line; HUVEC—human umbilical vein endothelial cells; IL—interleukin; iNOS—inducible nitric oxide synthase; LRP1—low-density lipoprotein-receptor-related protein 1; NGF—nerve growth factor; NF—κB-nuclear factor kappa-light-chain-enhancer of activated B cells; NO—nitric oxide; RAGE—receptor for advanced glycation end products; ROS—reactive oxygen species; tau—microtubule-associated protein; TNFα—tumor necrosis factor alpha; VDR—the vitamin D receptor.