Table 2.
The relationships of Alzheimer's disease susceptibility genes with vitamin A. NF = none found.
| Gene | Name | Relationships with vitamin A |
|---|---|---|
| Transport and entry | ||
| ALB | Albumin | Together with retinol binding protein forms the retinol transporter [39] |
| APOE | Apolipoprotein E | Expression regulated by LXR/RXR dimers [40] Involved in retinyl palmitate transport [41] |
| TTR | Transthyretin (prealbumin, amyloidosis type I) | Carrier protein for the retinol binding protein [42] |
| APOA1 | Apolipoprotein A-I | RORA target [43]: associates with transthyretin in plasma [44] |
| HSPG2 | Perlecan: (heparan sulfate proteoglycan 2) | Binds to transthyretin [45] |
| A2M | Alpha-2-macroglobulin | Synthesis decreased in vitamin-A- deficient rats [46] |
| ABCA1 | ATP-binding cassette, subfamily A (ABC1), member 1 | 22R-hydroxycholesterol and 9-cis-retinoic acid induce ABCA1 expression and cholesterol efflux in brain cells and decrease Beta-amyloid secretion [47]. Involved in retinol and alpha- and gamma-tocopherol transport [48, 49] |
| CLU | Clusterin (APOJ) LRP2 ligand | The clusterin promoter contains a RARE sequence: Expression is suppressed by all-trans-retinoic acid [50]. Vitamin A deficiency increases clusterin expression in sertoli cells [51] |
| LRP2 | Low density lipoprotein-related protein 2 (clusterin receptor) | Mediates the endocytosis of retinol via binding to retinol binding proteins and transthyretin [52, 53] |
| LRPAP1 | Low density lipoprotein receptor-related protein associated protein 1 | Regulates the uptake of retinol by LRP2 [54] |
|
| ||
| Metabolism | ||
| ALDH2 | Aldehyde dehydrogenase 2 family (mitochondrial) | Exhibits low NAD(+)-dependent retinaldehyde activity [55]: regulated by RARB [56] |
| CYP46A1 | Cytochrome P450, family 46, subfamily A, polypeptide 1 | Synthesises 24-S hydroxycholesterol, a ligand for RARA and RARG [57] |
| GSTM1 | Glutathione S-transferase M1 | Weakly catalyses the enzymic isomerization of 13-cis-retinoic acid to all-trans-retinoic acid [58] |
| GSTP1 | Glutathione S-transferase pi | Catalyses the enzymic isomerization of 13-cis-retinoic acid to all-trans-retinoic acid [58] |
| LIPA | Lipase A, lysosomal acid, cholesterol esterase (Wolman disease) | Metabolises carotenoid mono- and diesters providing a source of free carotenoids in the gut [59] |
| LPL | Lipoprotein lipase | Metabolises retinyl esters [60]. RORA target [61] |
| LRAT | Lecithin retinol acyltransferase (phosphatidylcholine—retinol O-acyltransferase) | Lecithin retinol acyltransferase (phosphatidylcholine—retinol O-acyltransferase) |
| MEF2A | Myocyte enhancer factor 2A | Regulates beta-carotene 15,15′-monooxygenase 1 which cleaves beta-carotene to all-trans retinal and is the key enzyme in the intestinal metabolism of carotenes to vitamin A [62] |
|
| ||
| Receptors, coreceptors and receptor binding partners | ||
| CHD4 | Chromodomain helicase DNA binding protein 4 | Binds to RORG [63] |
| ESR1 | Estrogen receptor 1 | Dimerises with RAR and RXRA [52] |
| KLF5 | Kruppel-like factor 5 (intestinal) | Binds to RARA [64] |
| NPAS2 | Neuronal PAS domain protein 2 | RAR alpha and RXR alpha bind to CLOCK and NPAS2 [65]. RORA target [66] |
| NR1H2 | Nuclear receptor subfamily 1, group H, member 2: liver X receptor beta | LXRs form obligate heterodimers with retinoid X receptors RARA, RXRA, RXRB, RXRG (Entrez gene) |
| PARP1 | Poly (ADP-ribose) polymerase family, member 1 | Interacts with RARB [67] |
| PIN1 | Protein (peptidylprolyl cis/trans isomerase) NIMA-interacting 1 | RARalpha directly interacts with Pin1. Overexpression of Pin1 inhibits ligand-dependent activation of RARalpha [68] |
| POU2F1 | POU class 2 homeobox 1 | Binds to RXR [69] |
| PPARA | Peroxisome proliferator-activated receptor alpha | Dimerises with RXRA and RXRG receptors [70] |
| PPARG | Peroxisome proliferator-activated receptor gamma | Dimerises with RXRA receptors [71] |
| RXRA | Retinoid X receptor, alpha | Retinoic acid receptor |
| THRA | Thyroid hormone receptor, alpha (erythroblastic leukemia viral (v-erb-a) oncogene homolog, avian) | Dimerises with RXRA [72] |
| UBQLN1 | Ubiquilin 1 | Binds to retinoic acid receptor alpha [73] |
| VDR | Vitamin D (1,25-dihydroxyvitamin D3) receptor | Heterodimerises with RXR and RARG [74] |
|
| ||
| APP and tau processing | ||
| APP | Amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | A gamma 57 gamma secretase cleavage product suppresses retinoid signalling [75] |
| BACE1 | Beta-site APP-cleaving enzyme 1 | Regulated by all-trans-retinoic acid [76] |
| NCSTN | Nicastrin | Blocks the effects of retinoic acid on neurogenesis [77] |
| PSEN1 | Presenilin 1 (Alzheimer disease 3) | Regulated by and regulates the effects of retinoic acid on neuronal differentiation [78, 79] |
| PSEN2 | Presenilin 2 (Alzheimer disease 4) | Activated by all-trans-retinoic acid in osteoblasts [80] |
| CDK5 | Cyclin-dependent kinase 5 | Activated by retinoic acid [81] |
| GSK3B | Glycogen synthase kinase 3 beta | SH-SY5Y cells differentiate to neuron-like cells when treated with Retinoic acid/BDNF leading to increases in tau and tau phosphorylation, mediated primarily by GSK3B [82]: GSK3B inhibitors inhibit RARbeta-induced adipogenesis in mouse embryonic stem cells [83]. |
| MAPT | Microtubule-associated protein tau | Phosphorylation of tau at the 12E8 (Ser-262/Ser-356) epitope decreased in retinoic acid treated cells: increased at Ser-195/Ser-198/Ser-199/Ser-202) and (Ser-396/Ser-404) [84] |
|
| ||
| Viral and bacterial defence RIG-1, PKR, NOD and Toll receptor signalling | ||
| CARD8 | Caspase recruitment domain family, member 8 | NF |
| CD14 | CD14 molecule | Expression regulated by retinoids [85]: binds to H. Pylori lipopolysaccharide [86]. |
| CD86 | CD86 molecule | Expression modulated by and the viral DNA minic polyriboinosinic:polyribocytidylic acid [87] |
| CST3 | Cystatin C | NF antimicrobial peptide [88] |
| DEFB122 | Defensin, beta 122: Antimicrobial peptide | NF |
| EIF2AK2 | Eukaryotic translation initiation factor 2-alpha kinase 2: (PKR activated by viral DNA) | Upregulated by retinoic acid in HL-60 leukemia cells [89] |
| GBP2 | Guanylate binding protein 2, interferon inducible | NF |
| MEFV | Mediterranean fever | NF |
| MPO | Myeloperoxidase | Antimicrobial peptide [88], expression regulated by RXR/PPAR gamma heterodimer [90] |
| PIN1 | peptidylprolyl cis/trans isomerase, NIMA-interacting 1 | Binds to and negatively regulates IRF3 [91] |
| TF | Transferrin | Antimicrobial peptide [88]. Vitamin A deficiency is associated with modified iron homeostasis that can be reversed by retinoid supplementation, TF contains a peroxisome proliferator-activated receptor-retinoic acid X receptor heterodimer binding site [92] |
| TRAF2 | TNF receptor-associated factor 2 | Infection with RNA viruses activates the cytoplasmic retinoic acid-inducible gene-I (RIG-I) pathway which activates transcription factor IRF-3 which in turn induces many antiviral genes. It also induces apoptosis via TRAF2 [25] |
| TLR4 | Toll-like receptor 4 | Expression suppressed by retinoic acid [93] |
| PVRL2 | Poliovirus receptor-related 2 (herpesvirus entry mediator B) | NF: herpes simplex receptor |
| ZBP1 | Z-DNA binding protein 1: DNA-dependent activator of interferon regulatory factors | NF |
|
| ||
| Cholesterol lipoprotein networks and lipid rafts | ||
| ABCA1 | Retinol transporter (see above) | |
| ABCG1 | ATP-binding cassette, subfamily G (WHITE), member 1 | Expression regulated by 9-cis retinoic acid and 22-hydroxycholesterol [94] |
| APOA5 | Apolipoprotein A-V | Regulated by RORA [95]. APOA5 polymorphisms modify lipoprotein bound retinyl palmitate concentrations [96] |
| APOC2 | Apolipoprotein C-II | Expression regulated by 9-cis-retinoic acid [97]. |
| APOC3 | Apolipoprotein C-III | RORA target [43] |
| APOC4 | Apolipoprotein C-IV | Expression regulated by RXR ligands [98] |
| APOD | Apolipoprotein D | Expression regulated by RARA [99] |
| CETP | Cholesteryl ester transfer protein, plasma | Expression induced by 9-cis retinoic acid (RXR agonist) [100] |
| FDPS | Farnesyl diphosphate synthase (farnesyl pyrophosphate synthetase, dimethylallyltranstransferase, geranyltranstransferase) | Activated by the LXR/retinoid X receptor dimer [101] |
| LPA | Lipoprotein, Lp(a) | Isotretinoin reduces LPA serum levels [102] |
| LDLR | Low-density lipoprotein receptor (familial hypercholesterolemia) | NF |
| LRP1 | Low-density lipoprotein-related protein 1 (alpha-2-macroglobulin receptor) | NF |
| LRP2 | See above (retinol receptor) | |
| LRP6 | Low-density lipoprotein receptor-related protein 6 | Expression induced by retinoic acid [103] |
| LRP8 | Low-density lipoprotein receptor-related protein 8, apolipoprotein e receptor | NF |
| NPC1 | Niemann-Pick disease, type C1 | NF |
| NPC2 | Niemann-Pick disease, type C2 | NF |
| OLR1 | Oxidized low-density lipoprotein (lectin-like) receptor 1 | NF |
| RFTN1 | Raftlin, lipid raft linker 1 | NF |
| SOAT1 | sterol O-acyltransferase 1: cholesterol acyltransferase | NF |
| SREBF1 | Sterol regulatory element binding transcription factor 1 | Liver X receptor/RXR target [104] |
| VLDLR | Very-low-density lipoprotein receptor | All-trans retinoic acid increases expression in adenocarcinoma cells [105] |
|
| ||
| Chemokines and cytokines and inflammation | ||
| AGER | Advanced glycosylation end product-specific receptor | Expression upregulated by retinol and vitamin A [106, 107] |
| ALOX5 | Arachidonate 5-lipoxygenase | RORA target [108] |
| CCL2 | Chemokine (C-C motif) ligand 2 | All-trans-retinoic acid suppresses bacterial lipopolysaccharide-induced expression and release in astrocytes [109] |
| CCL3 | Chemokine (C-C motif) ligand 3 | See CCL2 above |
| CCR2 | Chemokine (C-C motif) receptor 2 | Expression regulated by 9-cis-Retinoic acid [110] |
| IL10 | Interleukin 10 | All trans-retinoic acid increases IL10 production in monocytes and macrophages [111] |
| IL18 | Interleukin 18 (interferon-gamma-inducing factor) | Differentiation of SH-SY5Y neuroblastoma cells by all-trans retinoic acid activates IL18 [112]. |
| IL1A | Interleukin 1, alpha | Retinoic acid decreases expression in thymic epithelial cells [113] |
| IL1B | Interleukin 1, beta | Intraperitoneal retinoic acid reduces IL-1β, IL-6 and TNFα mRNA levels in the spinal cord after injury [114]. All-trans-retinoic acid increases IL1B expression in human aortic smooth muscle cells [115] |
| IL33 | Interleukin 33 | NF |
| IL6 | Interleukin 6 (interferon, beta 2) | Retinoic acid increases expression in thymic epithelial cells [113]. |
| IL8 | Interleukin 8 | Retinoid administration decreases polymorphonuclear neutrophilic leukocyte accumulation in mammary alveoli activated by lipopolysaccharide, and decreases IL-8 serum levels [116] |
| IL1RN | interleukin 1 receptor antagonist | Retinoic acid enhances IL-1 beta and inhibited IL-1ra production in 4beta phorbol 12beta-myristate-13alpha acetate - and lipopolysaccharide-activated human alveolar macrophages [117]. |
| PTGS2 | Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) | Suppressed by RARB [118] |
| TGFB1 | Transforming growth factor, beta 1 | Repressed by RXRA.PPARG dimers [119] |
| TNF | Tumor necrosis factor (TNF superfamily, member 2) | LPS from bacterial pathogens activates Retinoic inducible gene RIG-I which plays a key role in the expression of TNF-alpha in macrophages in response to LPS stimulation [120] |
| FAS | Fas (TNF receptor superfamily, member 6) | Retinoic acid increases the expression of FAS in adipocytes: all-trans retinoid acid reduces FAS expression in HELA cells |
|
| ||
| Complement and immune system | ||
| C4A | Complement component 4A (Rodgers blood group) | Complement C4 levels correlate with those of retinol in plasma [121] |
| C4B | Complement component 4B (Chido blood group) | See above |
| CFH | Complement factor H | Expression controlled by RAR beta [122] |
| CLU | Clusterin | See above |
| CR1 | Complement component (3b/4b) receptor 1 (Knops blood group) | NF |
| CRP | C-reactive protein, pentraxin related | Serum CRP levels negatively correlate with vitamin A levels [123] |
| CD33 | CD33 molecule | NF |
| CD36 | CD36 molecule (thrombospondin receptor) | RORA target [61] |
| HLA-A | Major histocompatibility complex, class I, A | Upregulated by differentiation of teratoma cells into neuronal cells by retinoic acid [124] |
| HLA-A2 | Major histocompatibility complex, class I, A2 | Upregulated by interferon alpha-2b and retinoic acid combined treatment in cervical cancer cells [125] |
| MICA | MHC class I polypeptide-related sequence A | Expression upregulated by retinoic acid in hepatic carcinoma cells [126] |
|
| ||
| Oestrogen and androgen related | ||
| AR | Androgen receptor (dihydrotestosterone receptor; testicular feminization; spinal and bulbar muscular atrophy; Kennedy disease) | |
| ESR1 | See above | |
| ESR2 | Estrogen receptor 2 (ER beta) | 9-cis retinoic acid stimulates expression in breast cancer cells [127] |
| CYP19A1 | Cytochrome P450, family 19, subfamily A, polypeptide 1: aromatase: estrogen synthase | Activated by RORA [128] |
| HSD11B1 | Hydroxysteroid (11-beta) dehydrogenase 1 | NF |
|
| ||
| Growth factor networks | ||
| BDNF | Brain-derived neurotrophic factor | Expression regulated by RARalpha/beta and vitamin A [129, 130], but all-trans retinoic acid reduces BDNF and TrkB gene expression in SH-SY5Y cells [131] |
| CSK | C-src tyrosine kinase | CSK negatively regulates RAR functions in relation to neurite differentiation [132] |
| FGF1 | Fibroblast growth factor 1 (acidic) | Protects fibroblasts from apoptosis induced by retinoid CD437 [133] |
| GAB2 | GRB2-associated binding protein 2 | Gab2 silencing results in hypersensitivity to retinoic acid -induced apoptosis in neuronal cells [134] |
| IGF1 | Insulin-like growth factor 1 (somatomedin C) | Pulmonary expression reduced in RORalpha knockout mice [135] |
| NTRK1 | Neurotrophic tyrosine kinase, receptor, type 1 | Retinoic acid restores adult hippocampal neurogenesis and reverses spatial memory deficit in vitamin-A-deprived rats, partly by upregulating NTRK1 (TrkA) [136] |
| NTRK2 | Neurotrophic tyrosine kinase, receptor, type 2 | All-trans retinoic acid reduces BDNF and TrkB gene expression in SH-SY5Y cells [131] |
| VEGFA | vascular endothelial growth factor A | Expression regulated by retinoid acid [137] |
| Other signalling | ||
| DKK1 | Dickkopf homolog 1 (Xenopus laevis) | Expression regulated by retinoic acid in stem cells [103] |
| DPYSL2 | Dihydropyrimidinase-like 2 | Upregulated in cortex and hippocampus by Vitamin A depletion [138] |
|
| ||
| Homocysteine and methionine metabolism | ||
| BLMH | Bleomycin hydrolase | Hydrolyses homocysteine thiolactone [139] |
| CBS | Cystathionine-beta-synthase | Converts homocysteine to cystathionine suppressed by all-trans-retinoic acid [140] |
| MSRA | methionine sulfoxide reductase A | Regulated by retinoic acid via two promoters including RARA [141] |
| MTHFD1L | Methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1-like | NF |
| MTHFR | 5,10-methylenetetrahydrofolate reductase (NADPH) | Methylenetetrahydrofolate reductase activity is suppressed in retinol-fed rats [142] |
| MTR | 5-methyltetrahydrofolate-homocysteine methyltransferase | In rats, a retinol-rich diet enhances the folate-dependent oxidation to CO2 of formate and histidine. The activity of hepatic methylenetetrahydrofolate reductase, which regulates liver folate metabolism, is suppressed, leading to decreased 5-methyltetrahydrofolate synthesis [142] |
| MTRR | 5-methyltetrahydrofolate-homocysteine methyltransferase reductase | NF |
| PON1 | Paraoxonase 1 | Hydrolyses homocysteine thiolactone [143]: vitamin A deficiency reduced serum PON1 activity in rats [144]. |
|
| ||
| Oxidative stress, Iron and mitochondria | ||
| COX1 | Mitochondrially encoded cytochrome c oxidase I | 9-cis retinoic acid treatment increases mitochondrial DNA transcription, including ND1, ND6, and COX1 [145] |
| COX2 | Mitochondrially encoded cytochrome c oxidase II | Expression increased by all-trans retinoic acid [146] |
| GAPDH | Glyceraldehyde-3-phosphate dehydrogenase | Retinoic acid target [147] |
| GSTM3 | Glutathione S-transferase M3 (brain) | Contains a retinoid X receptor-binding site [148] |
| HBG2 | Hemoglobin, gamma G | Vitamin A increases haemoglobin concentrations in children [149] |
| HFE | hemochromatosis | Neuroblastoma cells carrying the C282Y HFE variant do not differentiate when exposed to retinoic acid [150] |
| HMOX1 | Heme oxygenase (decycling) 1 | The increase in the expression of heme oxygenase-1 and the growth arrest and DNA damage-inducible transcription factor 153 caused by reactive oxygen species is blocked by aRARalpha-specific antagonist AGN194301 in retinal epithelial cells [151] |
| ND1 | NADH dehydrogenase subunit 1 | 9-cis retinoic acid treatment increases mitochondrial DNA transcription, including ND1, ND6, and COX1 [145] |
| ND4 | NADH dehydrogenase subunit 4 | Upregulated by all-trans retinoic acid in neutrophils [152] |
| ND6 | NADH dehydrogenase subunit 6 | 9-cis retinoic acid treatment increases mitochondrial DNA transcription, including ND1, ND6, and COX1 [145] |
| NFE2L2 | Nuclear factor (erythroid-derived 2)-like 2 | Inhibited by retinoic acid via RARalpha resulting in lack of expression of Nrf2 target genes [153] in mammary cells, but retinoic acid and 12-O-tetradecanoylphorbol acetate are also able to induce Nrf2 and its target gene NAD(P)H quinone oxidoreductase 1 in the SH-SY5Y neuroblastoma cell line [154]. |
| NOS1 | Nitric oxide synthase 1 (neuronal) | Expression regulated by retinoic acid [84] |
| NOS2 | Nitric oxide synthase 2, inducible | Ditto |
| NOS3 | Nitric oxide synthase 3 (endothelial cell) | Ditto |
| NQO1 | NAD(P)H dehydrogenase, quinone 1 | Retinoic acid (RA) and 12-O-tetradecanoylphorbol acetats are able to induce Nrf2 and its target gene NAD(P)H quinone oxidoreductase 1 in the SH-SY5Y neuroblastomacell line [154] |
| SOD2 | Superoxide dismutase 2, mitochondrial | All-trans-retinoic acid induces manganese superoxide dismutase in a human neuroblastoma cell line [155] |
| PCK1 | Phosphoenolpyruvate carboxykinase 1 (soluble) | Three RXR-binding elements (retinoic acid response element (RARE)1/PCK1, RARE2, and RARE3/PCK2) are located in the promoter of Pck1 [156] |
| PON2 | Paraoxonase 2 | NF |
| PON3 | Paraoxonase 3 | NF |
| TFAM | Transcription factor A, mitochondrial | Levels are increased by vitamin A [157] |
|
| ||
| Heat shock | ||
| DNAJC28 | DnaJ (Hsp40) homolog, subfamily C, member 28 | NF |
| HSPA1B | Heat shock 70 kDa protein 1B | NF |
| HSPA5 | Heat shock 70 kDa protein 5 (glucose-regulated protein, 78 kDa) | Endoplasmic reticulum stress is increased in hepatocarcinoma cells by all-trans retinoic acid, characterised by increased expression of HSPA5 (grp78), GADD153, and XBP1[158] |
|
| ||
| Monoamine networks | ||
| ADRB1 | Adrenergic, beta-1-, receptor | RARA target [159] |
| ADRB2 | Adrenergic, beta-2-, receptor, surface | Expression regulated by all-trans retinoic acid [160] |
| COMT | Catechol-O-methyltransferase | Expression stimulated by all-trans retinoic acid [161] |
| PNMT | Phenylethanolamine N-methyltransferase | Retinoic acid differentiates embryonic carcinoma cells into neuronal cells, 70% of which stain for tyrosine hydroxylase, dopamine beta-hydroxylase, and phenylethanolamine N-methyltransferase [162]. |
|
| ||
| Cholinergic | ||
| CHAT | Choline acetyltransferase | Expression controlled by retinoic acid [163] |
| CHRNA3 | Cholinergic receptor, nicotinic, alpha 3 | Expression increased by retinoid acid [164] |
| CHRNA4 | Cholinergic receptor, nicotinic, alpha 4 | Expression decreased by retinoic acid [164] |
| CHRNB2 | Cholinergic receptor, nicotinic, beta 2 (neuronal) | Expression increased by retinoid acid [164] |
|
| ||
| Neuropeptide | ||
| GRN | Granulin | All-trans retinoic acid increases expression in myeloid cells [165] |
|
| ||
| Adhesion and proteoglycans | ||
| ACAN | Aggrecan | Expression modulated by 13-cis retinoic acid in fibroblasts [166] |
| ICAM1 | Intercellular adhesion molecule 1 (CD54), human rhinovirus receptor | All-trans retinoic acid downregulates ICAM1 expression in bone marrow stromal cells [167] |
|
| ||
| Structural, dynamins, and kinesins | ||
| COL11A1 | Collagen, type XI, alpha 1 | Expression controlled by all-trans-retinoic acid [168] |
| DSC1 | Desmocollin 1 | Retinoic acid decreases expression in oral keratinocytes [169] |
| LMNA | Lamin A/C (nuclear) | Promoter contains a retinoic acid-responsive element (L-RARE) [170] |
|
| ||
| Ubiquitin | ||
| UBD | Ubiquitin D | All-trans retinoic acid activated the ubiquitin/proteasome pathway in human acute myeloid leukemia cell lines [171] |
| UBE2I | Ubiquitin-conjugating enzyme E2I (UBC9 homolog, yeast) | See above |
|
| ||
| DNA repair | ||
| XRCC1 | X-ray repair complementing defective repair in Chinese hamster cells 1 | N-[4-hydroxyphenyl] retinamide induces apoptosis in bladder cancer cell line and downregulates XRCC1 [172] |
|
| ||
| Cell cycle and tumour | ||
| CDC2 | Cell division cycle 2, G1 to S, and G2 to M | Activated by retinoic acid [173] |
|
| ||
| Miscellaneous metabolism | ||
| ACAD8 | Acyl-coenzyme A dehydrogenase family, member 8 | Catalyzes the dehydrogenation of acyl-CoA derivatives in the metabolism of fatty acids or branch chained amino acids. The encoded protein is a mitochondrial enzyme that functions in catabolism of the branched-chain amino acid valine. |
| ALDH18A1 | Aldehyde dehydrogenase 18 family, member A1 | NF the encoded protein catalyzes the reduction of glutamate to delta1-pyrroline-5-carboxylate, a critical step in the de novo biosynthesis of proline, ornithine and arginine. |
| ARSA | Arylsulfatase A: hydrolyzes cerebroside sulfate to cerebroside and sulphate | Increased urinary excretion of both arylsulfatases A and B is increased in cases of severe vitamin A deficiency coupled with malnutrition [174] |
| ELAVL4 | ELAV (embryonic lethal, abnormal vision, drosophila)-like 4 (Hu antigen D) | Inhibition reduces retinoic acid-induced neuronal differentiation of mouse embryonal carcinoma P19 cells [175] |
| SGPL1 | Sphingosine-1-phosphate lyase 1 | Treatment of F9 embryonal carcinoma cells with retinoic acid induces differentiation to primitive endoderm (PrE). This effect is attenuated by SGPL1 knockout [176]. |
|
| ||
| Miscellaneous | ||
| CELF2 | CUGBP, Elav-like family member 2 | Splicing regulated by retinoic acid [177] |
| CUBN | Cubilin (intrinsic factor-cobalamin receptor) | Expression regulated by all-trans-retinoic acid [178] |
| F13A1 | Coagulation factor XIII, A1 polypeptide | Vitamin A reduces factor XIII levels in rats fed an atherogenic diet [179]. |
| HHEX | Hematopoietically expressed homeobox | All-trans retinoic acid enhances expression in normal and tumorous mammary tissue [180] |
| NEDD9 | Neural precursor cell expressed, developmentally downregulated 9 | Downstream target of all-trans retinoic acid and its receptors in the human SH-SY5Y neuroblastoma cell line [181] |
| RELN | Reelin | Retinoic acid-induced differentiation of NT2 cells to hNT neurons increases reelin expression [182]. |
| RNR1 | RNA, ribosomal 1 | NF |
| RPS3A | Ribosomal protein S3A | Downregulated by retinoid-induced differentiation of HL-60 cells [183] |
| RUNX1 | Runt-related transcription factor 1 (acute myeloid leukemia 1; aml1 oncogene) | RUNX1 knockdown inhibits retinoid-induced differentiation of HL-60 myeloid leukaemia cells [184]. |
| SEPT3 | Septin 3 | Expressed in SH-SY5Y, after retinoic acid-induced differentiation [185] |
| SNCA | Synuclein, alpha (non-A4 component of amyloid precursor) | Vitamin A, beta-carotene and coenzyme Q10 inhibit the formation of synuclein fibrils [186] |
| SYN3 | Synapsin III | Synapsins including SYN3 are upregulated by retinoic acid-induced differentiation of NTera-2cl.D1 cells [187] |
| TARDBP | TAR DNA binding protein | NF |
| VCP | Valosin-containing protein | Retinoic acid receptor responder (RARRES1) regulates VCP expression in human prostatic epithelial cells [188] |