Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation
Abstract
:1. Introduction
2. Results
2.1. Vitamin D Analogues Decrease Total Aβ Level
2.2. Analysis of Non-Amyloidogenic APP Shedding in Presence of Vitamin D Analogues
2.3. Vitamin D Analogues Decrease Amyloidogenic β-Secretase Dependent APP Cleavage
2.4. Vitamin D Analogues Decrease γ-Secretase Processing of APP
2.5. Vitamin D3 and Vitamin D2 Analogues Increase Aβ-Degradation
2.6. Influence of Vitamin D3 and Vitamin D2 Analogues on Inflammatory Processes
3. Discussion
4. Materials and Methods
4.1. Chemicals and Reagents
4.2. Cell Culture and Mice
4.3. Vitamin D Incubations
4.3.1. Cell Culture
4.3.2. Mouse Brains or Purified Membranes
4.4. Determination of Protein Concentration
4.5. Western Blot Experiments
4.6. Determination of Total Aβ-Degradation
4.6.1. Determination of Total Aβ-Degradation in N2a wt Cells.
4.6.2. Determination of Total Aβ-Degradation in Deficient Mouse Brains
4.7. Secretase Activity Assays
4.7.1. Determination of α-, β- and γ-Secretase Activity in Living SH-SY5Y Cells
4.7.2. Determination of β-Secretase Activity in Isolated SH-SY5Y Membranes
4.8. RT-PCR Experiments
4.9. Neprilysin Activity Assay
4.10. Enzyme-Linked Immunosorbent Assay (ELISA)
4.11. Lactate Dehydrogenase (LDH) Activity Assay
4.12. Data Analysis
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
- Glenner, G.G.; Wong, C.W. Alzheimer’s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophy. Res. Commun. 2012, 425, 534–539. [Google Scholar] [CrossRef] [PubMed]
- Masters, C.L.; Simms, G.; Weinman, N.A.; Multhaup, G.; McDonald, B.L.; Beyreuther, K. Amyloid plaque core protein in alzheimer disease and down syndrome. Proc. Natl. Acad. Sci. USA 1985, 82, 4245–4249. [Google Scholar] [CrossRef] [PubMed]
- Grundke-Iqbal, I.; Iqbal, K.; Tung, Y.C.; Quinlan, M.; Wisniewski, H.M.; Binder, L.I. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc. Natl. Acad. Sci. USA 1986, 83, 4913–4917. [Google Scholar] [CrossRef] [PubMed]
- Grundke-Iqbal, I.; Iqbal, K.; Quinlan, M.; Tung, Y.C.; Zaidi, M.S.; Wisniewski, H.M. Microtubule-associated protein tau. A component of alzheimer paired helical filaments. J. Biol. Chem. 1986, 261, 6084–6089. [Google Scholar] [PubMed]
- Sinha, S.; Anderson, J.P.; Barbour, R.; Basi, G.S.; Caccavello, R.; Davis, D.; Doan, M.; Dovey, H.F.; Frigon, N.; Hong, J.; et al. Purification and cloning of amyloid precursor protein β-secretase from human brain. Nature 1999, 402, 537–540. [Google Scholar] [CrossRef] [PubMed]
- Vassar, R.; Bennett, B.D.; Babu-Khan, S.; Kahn, S.; Mendiaz, E.A.; Denis, P.; Teplow, D.B.; Ross, S.; Amarante, P.; Loeloff, R.; et al. β-secretase cleavage of alzheimer’s amyloid precursor protein by the transmembrane aspartic protease bace. Science 1999, 286, 735–741. [Google Scholar] [CrossRef] [PubMed]
- Kimberly, W.T.; LaVoie, M.J.; Ostaszewski, B.L.; Ye, W.; Wolfe, M.S.; Selkoe, D.J. Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, aph-1, and pen-2. Proc. Natl. Acad. Sci. USA 2003, 100, 6382–6387. [Google Scholar] [CrossRef] [PubMed]
- Haass, C. Take five—BACE and the γ-secretase quartet conduct alzheimer’s amyloid β-peptide generation. EMBO J. 2004, 23, 483–488. [Google Scholar] [CrossRef] [PubMed]
- Buxbaum, J.D.; Liu, K.N.; Luo, Y.; Slack, J.L.; Stocking, K.L.; Peschon, J.J.; Johnson, R.S.; Castner, B.J.; Cerretti, D.P.; Black, R.A. Evidence that tumor necrosis factor α converting enzyme is involved in regulated α-secretase cleavage of the alzheimer amyloid protein precursor. J. Biol. Chem. 1998, 273, 27765–27767. [Google Scholar] [CrossRef] [PubMed]
- Lammich, S.; Kojro, E.; Postina, R.; Gilbert, S.; Pfeiffer, R.; Jasionowski, M.; Haass, C.; Fahrenholz, F. Constitutive and regulated α-secretase cleavage of alzheimer’s amyloid precursor protein by a disintegrin metalloprotease. Proc. Natl. Acad. Sci. USA 1999, 96, 3922–3927. [Google Scholar] [CrossRef] [PubMed]
- Kuhn, P.H.; Wang, H.; Dislich, B.; Colombo, A.; Zeitschel, U.; Ellwart, J.W.; Kremmer, E.; Rossner, S.; Lichtenthaler, S.F. Adam10 is the physiologically relevant, constitutive α-secretase of the amyloid precursor protein in primary neurons. EMBO J. 2010, 29, 3020–3032. [Google Scholar] [CrossRef] [PubMed]
- Koike, H.; Tomioka, S.; Sorimachi, H.; Saido, T.C.; Maruyama, K.; Okuyama, A.; Fujisawa-Sehara, A.; Ohno, S.; Suzuki, K.; Ishiura, S. Membrane-anchored metalloprotease MDC9 has an α-secretase activity responsible for processing the amyloid precursor protein. Biochem. J. 1999, 343, 371–375. [Google Scholar] [CrossRef] [PubMed]
- Iwata, N.; Tsubuki, S.; Takaki, Y.; Shirotani, K.; Lu, B.; Gerard, N.P.; Gerard, C.; Hama, E.; Lee, H.J.; Saido, T.C. Metabolic regulation of brain Aβ by neprilysin. Science 2001, 292, 1550–1552. [Google Scholar] [CrossRef] [PubMed]
- Farris, W.; Mansourian, S.; Chang, Y.; Lindsley, L.; Eckman, E.A.; Frosch, M.P.; Eckman, C.B.; Tanzi, R.E.; Selkoe, D.J.; Guenette, S. Insulin-degrading enzyme regulates the levels of insulin, amyloid β-protein, and the β-amyloid precursor protein intracellular domain in vivo. Proc. Natl. Acad. Sci. USA 2003, 100, 4162–4167. [Google Scholar] [CrossRef] [PubMed]
- Grimm, M.O.; Grimm, H.S.; Patzold, A.J.; Zinser, E.G.; Halonen, R.; Duering, M.; Tschape, J.A.; De Strooper, B.; Muller, U.; Shen, J.; et al. Regulation of cholesterol and sphingomyelin metabolism by amyloid-β and presenilin. Nature Cell Biol. 2005, 7, 1118–1123. [Google Scholar] [CrossRef] [PubMed]
- Grimm, M.O.; Kuchenbecker, J.; Grosgen, S.; Burg, V.K.; Hundsdorfer, B.; Rothhaar, T.L.; Friess, P.; de Wilde, M.C.; Broersen, L.M.; Penke, B.; et al. Docosahexaenoic acid reduces amyloid beta production via multiple pleiotropic mechanisms. J. Biol. Chem. 2011, 286, 14028–14039. [Google Scholar] [CrossRef] [PubMed]
- Grimm, M.O.; Zinser, E.G.; Grosgen, S.; Hundsdorfer, B.; Rothhaar, T.L.; Burg, V.K.; Kaestner, L.; Bayer, T.A.; Lipp, P.; Muller, U.; et al. Amyloid precursor protein (APP) mediated regulation of ganglioside homeostasis linking alzheimer’s disease pathology with ganglioside metabolism. PLoS ONE 2012, 7, e34095. [Google Scholar] [CrossRef] [PubMed]
- Osenkowski, P.; Ye, W.; Wang, R.; Wolfe, M.S.; Selkoe, D.J. Direct and potent regulation of gamma-secretase by its lipid microenvironment. J. Biol. Chem. 2008, 283, 22529–22540. [Google Scholar] [CrossRef] [PubMed]
- Grimm, M.O.; Rothhaar, T.L.; Grosgen, S.; Burg, V.K.; Hundsdorfer, B.; Haupenthal, V.J.; Friess, P.; Kins, S.; Grimm, H.S.; Hartmann, T. Trans fatty acids enhance amyloidogenic processing of the alzheimer amyloid precursor protein (APP). J. Nutr. Biochem. 2012, 23, 1214–1223. [Google Scholar] [CrossRef] [PubMed]
- Burg, V.K.; Grimm, H.S.; Rothhaar, T.L.; Grosgen, S.; Hundsdorfer, B.; Haupenthal, V.J.; Zimmer, V.C.; Mett, J.; Weingartner, O.; Laufs, U.; et al. Plant sterols the better cholesterol in alzheimer’s disease? A mechanistical study. J. Neurosci. 2013, 33, 16072–16087. [Google Scholar] [CrossRef] [PubMed]
- Lemkul, J.A.; Bevan, D.R. Aggregation of alzheimer’s amyloid β-peptide in biological membranes: A molecular dynamics study. Biochemistry 2013, 52, 4971–4980. [Google Scholar] [CrossRef] [PubMed]
- Grimm, M.O.; Haupenthal, V.J.; Mett, J.; Stahlmann, C.P.; Blumel, T.; Mylonas, N.T.; Endres, K.; Grimm, H.S.; Hartmann, T. Oxidized docosahexaenoic acid species and lipid peroxidation products increase amyloidogenic amyloid precursor protein processing. Neurodegener. Dis. 2016, 16, 44–54. [Google Scholar] [CrossRef] [PubMed]
- Rothhaar, T.L.; Grosgen, S.; Haupenthal, V.J.; Burg, V.K.; Hundsdorfer, B.; Mett, J.; Riemenschneider, M.; Grimm, H.S.; Hartmann, T.; Grimm, M.O. Plasmalogens inhibit app processing by directly affecting γ-secretase activity in alzheimer’s disease. Sci. World J. 2012, 2012, 141240. [Google Scholar] [CrossRef] [PubMed]
- Grimm, M.O.; Grimm, H.S.; Tomic, I.; Beyreuther, K.; Hartmann, T.; Bergmann, C. Independent inhibition of alzheimer disease β- and γ-secretase cleavage by lowered cholesterol levels. J. Biol. Chem. 2008, 283, 11302–11311. [Google Scholar] [CrossRef] [PubMed]
- Grimm, M.O.; Mett, J.; Stahlmann, C.P.; Haupenthal, V.J.; Blumel, T.; Stotzel, H.; Grimm, H.S.; Hartmann, T. Eicosapentaenoic acid and docosahexaenoic acid increase the degradation of amyloid-β by affecting insulin-degrading enzyme. Biochem. Cell Biol. 2016, 94, 534–542. [Google Scholar] [CrossRef] [PubMed]
- Pierucci, F.; Garcia-Gil, M.; Frati, A.; Bini, F.; Martinesi, M.; Vannini, E.; Mainardi, M.; Luzzati, F.; Peretto, P.; Caleo, M.; et al. Vitamin D3 protects against Aβ peptide cytotoxicity in differentiated human neuroblastoma SH-SY5Y cells: A role for S1P1/p38MAPK/ATF4 axis. Neuropharmacology 2017, 116, 328–342. [Google Scholar] [CrossRef] [PubMed]
- Raha, S.; Lee, H.J.; Yumnam, S.; Hong, G.E.; Saralamma, V.V.G.; Ha, Y.L.; Kim, J.O.; Kim, Y.S.; Heo, J.D.; Lee, S.J.; et al. Vitamin D2 suppresses amyloid-β 25–35 induced microglial activation in BV2 cells by blocking the NF-κB inflammatory signaling pathway. Life sci. 2016, 161, 37–44. [Google Scholar] [CrossRef] [PubMed]
- Guo, Y.X.; He, L.Y.; Zhang, M.; Wang, F.; Liu, F.; Peng, W.X. 1,25-dihydroxyvitamin D3 regulates expression of LRP1 and rage in vitro and in vivo, enhancing Aβ1–40 brain-to-blood efflux and peripheral uptake transport. Neuroscience 2016, 322, 28–38. [Google Scholar] [CrossRef] [PubMed]
- Grimm, M.O.; Lehmann, J.; Mett, J.; Zimmer, V.C.; Grosgen, S.; Stahlmann, C.P.; Hundsdorfer, B.; Haupenthal, V.J.; Rothhaar, T.L.; Herr, C.; et al. Impact of vitamin D on amyloid precursor protein processing and amyloid-β peptide degradation in alzheimer’s disease. Neurodegener. Dis. 2014, 13, 75–81. [Google Scholar] [CrossRef] [PubMed]
- Grimm, M.O.; Mett, J.; Hartmann, T. The impact of vitamin E and other fat-soluble vitamins on alzheimer’s disease. Int. J. Mol. Sci. 2016, 17, 1785. [Google Scholar] [CrossRef] [PubMed]
- Patel, P.; Shah, J. Role of vitamin D in amyloid clearance via LRP-1 upregulation in alzheimer’s disease: A potential therapeutic target? J. Chem. Neuroanat. 2017, 85, 36–42. [Google Scholar] [CrossRef] [PubMed]
- Jimenez-Jimenez, F.J.; Molina, J.A.; de Bustos, F.; Orti-Pareja, M.; Benito-Leon, J.; Tallon-Barranco, A.; Gasalla, T.; Porta, J.; Arenas, J. Serum levels of β-carotene, α-carotene and vitamin A in patients with alzheimer’s disease. Eur. J. Neurol. 1999, 6, 495–497. [Google Scholar] [CrossRef] [PubMed]
- Mangialasche, F.; Xu, W.; Kivipelto, M.; Costanzi, E.; Ercolani, S.; Pigliautile, M.; Cecchetti, R.; Baglioni, M.; Simmons, A.; Soininen, H.; et al. Tocopherols and tocotrienols plasma levels are associated with cognitive impairment. Neurobiol. aging 2012, 33, 2282–2290. [Google Scholar] [CrossRef] [PubMed]
- Lopes da Silva, S.; Vellas, B.; Elemans, S.; Luchsinger, J.; Kamphuis, P.; Yaffe, K.; Sijben, J.; Groenendijk, M.; Stijnen, T. Plasma nutrient status of patients with alzheimer’s disease: Systematic review and meta-analysis. Alzheimers Dement. 2014, 10, 485–502. [Google Scholar] [CrossRef] [PubMed]
- Presse, N.; Shatenstein, B.; Kergoat, M.J.; Ferland, G. Low vitamin k intakes in community-dwelling elders at an early stage of alzheimer’s disease. J. Am. Diet. Assoc. 2008, 108, 2095–2099. [Google Scholar] [CrossRef] [PubMed]
- Sato, Y.; Honda, Y.; Hayashida, N.; Iwamoto, J.; Kanoko, T.; Satoh, K. Vitamin K deficiency and osteopenia in elderly women with alzheimer’s disease. Arch. Phys. Med. Rehabil. 2005, 86, 576–581. [Google Scholar] [CrossRef] [PubMed]
- Annweiler, C.; Souberbielle, J.C.; Schott, A.M.; de Decker, L.; Berrut, G.; Beauchet, O. Vitamin D in the elderly: 5 points to remember. Geriatrie et Psychologie Neuropsychiatrie du Vieillissement 2011, 9, 259–267. [Google Scholar] [CrossRef] [PubMed]
- Annweiler, C.; Beauchet, O. Vitamin D-mentia: Randomized clinical trials should be the next step. Neuroepidemiology 2011, 37, 249–258. [Google Scholar] [CrossRef] [PubMed]
- Banerjee, A.; Khemka, V.K.; Ganguly, A.; Roy, D.; Ganguly, U.; Chakrabarti, S. Vitamin D and alzheimer’s disease: Neurocognition to therapeutics. Int. J. Alzheimers Dis. 2015, 2015, 192747. [Google Scholar] [CrossRef] [PubMed]
- Eyles, D.W.; Smith, S.; Kinobe, R.; Hewison, M.; McGrath, J.J. Distribution of the vitamin d receptor and 1 α-hydroxylase in human brain. J. Chem. Neuroanat. 2005, 29, 21–30. [Google Scholar] [CrossRef] [PubMed]
- Pardridge, W.M.; Sakiyama, R.; Coty, W.A. Restricted transport of vitamin D and a derivatives through the rat blood-brain barrier. J. Neurochem. 1985, 44, 1138–1141. [Google Scholar] [CrossRef] [PubMed]
- Gezen-Ak, D.; Atasoy, I.L.; Candas, E.; Alaylioglu, M.; Yilmazer, S.; Dursun, E. Vitamin D receptor regulates amyloid beta 1–42 production with protein disulfide isomerase A3. ACS Chem. Neurosci. 2017, 8, 2335–2346. [Google Scholar] [CrossRef] [PubMed]
- Brown, A.J. Therapeutic uses of vitamin D analogues. Am. J. Kidney Dis. 2001, 38, S3–S19. [Google Scholar] [CrossRef] [PubMed]
- Mazzaferro, S.; Goldsmith, D.; Larsson, T.E.; Massy, Z.A.; Cozzolino, M. Vitamin D metabolites and/or analogs: Which D for which patient? Curren. Vasc. Pharmacol. 2014, 12, 339–349. [Google Scholar] [CrossRef]
- Rohan de Silva, H.A.; Jen, A.; Wickenden, C.; Jen, L.S.; Wilkinson, S.L.; Patel, A.J. Cell-specific expression of β-amyloid precursor protein isoform mrnas and proteins in neurons and astrocytes. Mol. Brain Res. 1997, 47, 147–156. [Google Scholar] [CrossRef]
- Wootton, A.M. Improving the measurement of 25-hydroxy vitamin D. Clin. Biochemist. Rev. 2005, 26, 33–36. [Google Scholar]
- Vieth, R. Why the minimum desirable serum 25-hydroxy vitamin D level should be 75 nmol/L (30 ng/mL). Best Pract. Res. Clin. Endocrinol. 2011, 25, 681–691. [Google Scholar] [CrossRef] [PubMed]
- Kennel, K.A.; Drake, M.T.; Hurley, D.L. Vitamin D deficiency in adults: When to test and how to treat. Mayo Clin. Proc. 2010, 85, 752–757. [Google Scholar] [CrossRef] [PubMed]
- Wu-Wong, J.R.; Nakane, M.; Gagne, G.D.; Brooks, K.A.; Noonan, W.T. Comparison of the pharmacological effects of paricalcitol and doxercalciferol on the factors involved in mineral homeostasis. Int. J. Endocrinol. 2010, 2010, 621687. [Google Scholar] [CrossRef] [PubMed]
- Piotrowska, A.; Wierzbicka, J.; Nadkarni, S.; Brown, G.; Kutner, A.; Zmijewski, M.A. Antiproliferative activity of double point modified analogs of 1,25-dihydroxyvitamin D(2) against human malignant melanoma cell lines. Int. J. Mol. Sci. 2016, 17, 76. [Google Scholar] [CrossRef] [PubMed]
- Brandi, M.L. Indications on the use of vitamin D and vitamin D metabolites in clinical phenotypes. Clin. Cases Miner. Bone Metab. 2010, 7, 243–250. [Google Scholar] [PubMed]
- Duplancic, D.; Cesarik, M.; Poljak, N.K.; Radman, M.; Kovacic, V.; Radic, J.; Rogosic, V. The influence of selective vitamin D receptor activator paricalcitol on cardiovascular system and cardiorenal protection. Clin. Interv. Aging 2013, 8, 149–156. [Google Scholar] [PubMed]
- Dinarello, C.A. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 2011, 117, 3720–3732. [Google Scholar] [CrossRef] [PubMed]
- Cacabelos, R.; Alvarez, X.A.; Fernandez-Novoa, L.; Franco, A.; Mangues, R.; Pellicer, A.; Nishimura, T. Brain interleukin-1 β in alzheimer’s disease and vascular dementia. Methods Find. Exp. Clin. Pharmacol. 1994, 16, 141–151. [Google Scholar] [PubMed]
- Perez-Lopez, F.R.; Chedraui, P.; Fernandez-Alonso, A.M. Vitamin D and aging: Beyond calcium and bone metabolism. Maturitas 2011, 69, 27–36. [Google Scholar] [CrossRef] [PubMed]
- Amer, M.; Qayyum, R. Relation between serum 25-hydroxyvitamin D and c-reactive protein in asymptomatic adults (from the continuous national health and nutrition examination survey 2001 to 2006). Am. J. Cardiol. 2012, 109, 226–230. [Google Scholar] [CrossRef] [PubMed]
- Cannell, J.J.; Hollis, B.W.; Zasloff, M.; Heaney, R.P. Diagnosis and treatment of vitamin D deficiency. Expert Opin. Pharmacother. 2008, 9, 107–118. [Google Scholar] [CrossRef] [PubMed]
- McGrath, J. Hypothesis: Is low prenatal vitamin D a risk-modifying factor for schizophrenia? Schizophr. Res. 1999, 40, 173–177. [Google Scholar] [CrossRef]
- Annweiler, C. Vitamin D-mentia: Is vitamin D optional or essential for preventing late-life cognitive decline? J. Am. Geriatr. Soc. 2017, 65, 2155–2157. [Google Scholar] [CrossRef] [PubMed]
- Lemire, P.; Brangier, A.; Beaudenon, M.; Duval, G.T.; Annweiler, C. Cognitive changes under memantine according to vitamin D status in alzheimer patients: An exposed/unexposed cohort pilot study. J. Steroid Biochem. Mol. Biol. 2016, 175, 151–156. [Google Scholar] [CrossRef] [PubMed]
- Etgen, T.; Sander, D.; Bickel, H.; Sander, K.; Forstl, H. Vitamin D deficiency, cognitive impairment and dementia: A systematic review and meta-analysis. Dement. Geriatr. Cogn. 2012, 33, 297–305. [Google Scholar] [CrossRef] [PubMed]
- Van der Schaft, J.; Koek, H.L.; Dijkstra, E.; Verhaar, H.J.; van der Schouw, Y.T.; Emmelot-Vonk, M.H. The association between vitamin D and cognition: A systematic review. Ageing Res. Rev. 2013, 12, 1013–1023. [Google Scholar] [CrossRef] [PubMed]
- Dickens, A.P.; Lang, I.A.; Langa, K.M.; Kos, K.; Llewellyn, D.J. Vitamin D, cognitive dysfunction and dementia in older adults. CNS Drugs 2011, 25, 629–639. [Google Scholar] [CrossRef] [PubMed]
- Annweiler, C.; Allali, G.; Allain, P.; Bridenbaugh, S.; Schott, A.M.; Kressig, R.W.; Beauchet, O. Vitamin D and cognitive performance in adults: A systematic review. Eur. J. Neurol. 2009, 16, 1083–1089. [Google Scholar] [CrossRef] [PubMed]
- Sutherland, M.K.; Wong, L.; Somerville, M.J.; Yoong, L.K.; Bergeron, C.; Parmentier, M.; McLachlan, D.R. Reduction of calbindin-28k mrna levels in alzheimer as compared to huntington hippocampus. Mol. Brain Res. 1993, 18, 32–42. [Google Scholar] [CrossRef]
- Balion, C.; Griffith, L.E.; Strifler, L.; Henderson, M.; Patterson, C.; Heckman, G.; Llewellyn, D.J.; Raina, P. Vitamin D, cognition, and dementia: A systematic review and meta-analysis. Neurology 2012, 79, 1397–1405. [Google Scholar] [CrossRef] [PubMed]
- Afzal, S.; Bojesen, S.E.; Nordestgaard, B.G. Reduced 25-hydroxyvitamin d and risk of alzheimer’s disease and vascular dementia. Alzheimers Dement. 2014, 10, 296–302. [Google Scholar] [CrossRef] [PubMed]
- Littlejohns, T.J.; Henley, W.E.; Lang, I.A.; Annweiler, C.; Beauchet, O.; Chaves, P.H.; Fried, L.; Kestenbaum, B.R.; Kuller, L.H.; Langa, K.M.; et al. Vitamin D and the risk of dementia and alzheimer disease. Neurology 2014, 83, 920–928. [Google Scholar] [CrossRef] [PubMed]
- Mokry, L.E.; Ross, S.; Morris, J.A.; Manousaki, D.; Forgetta, V.; Richards, J.B. Genetically decreased vitamin D and risk of alzheimer disease. Neurology 2016, 87, 2567–2574. [Google Scholar] [CrossRef] [PubMed]
- Yu, J.; Gattoni-Celli, M.; Zhu, H.; Bhat, N.R.; Sambamurti, K.; Gattoni-Celli, S.; Kindy, M.S. Vitamin D3-enriched diet correlates with a decrease of amyloid plaques in the brain of AβPP transgenic mice. J. Alzheimer’s Dis. 2011, 25, 295–307. [Google Scholar]
- Koh, Y.H.; von Arnim, C.A.; Hyman, B.T.; Tanzi, R.E.; Tesco, G. Bace is degraded via the lysosomal pathway. J. Biol. Chem. 2005, 280, 32499–32504. [Google Scholar] [CrossRef] [PubMed]
- Qing, H.; Zhou, W.; Christensen, M.A.; Sun, X.; Tong, Y.; Song, W. Degradation of bace by the ubiquitin-proteasome pathway. FASEB J. 2004, 18, 1571–1573. [Google Scholar] [CrossRef] [PubMed]
- Alvarez-Diaz, S.; Larriba, M.J.; Lopez-Otin, C.; Munoz, A. Vitamin D: Proteases, protease inhibitors and cancer. Cell Cycle 2010, 9, 32–37. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, M.; Deng, Y.; Luo, Y.; Zhang, S.; Zou, H.; Cai, F.; Wada, K.; Song, W. Control of BACE1 degradation and APP processing by ubiquitin carboxyl-terminal hydrolase L1. J. Neurochem. 2012, 120, 1129–1138. [Google Scholar] [CrossRef] [PubMed]
- Max, D.; Brandsch, C.; Schumann, S.; Kuhne, H.; Frommhagen, M.; Schutkowski, A.; Hirche, F.; Staege, M.S.; Stangl, G.I. Maternal vitamin D deficiency causes smaller muscle fibers and altered transcript levels of genes involved in protein degradation, myogenesis, and cytoskeleton organization in the newborn rat. Mol. Nutr. Food Res. 2014, 58, 343–352. [Google Scholar] [CrossRef] [PubMed]
- Briones, T.L.; Darwish, H. Vitamin D mitigates age-related cognitive decline through the modulation of pro-inflammatory state and decrease in amyloid burden. J. Neuroinflamm. 2012, 9, 244. [Google Scholar] [CrossRef] [PubMed]
- Takasugi, N.; Tomita, T.; Hayashi, I.; Tsuruoka, M.; Niimura, M.; Takahashi, Y.; Thinakaran, G.; Iwatsubo, T. The role of presenilin cofactors in the γ-secretase complex. Nature 2003, 422, 438–441. [Google Scholar] [CrossRef] [PubMed]
- Dries, D.R.; Yu, G. Assembly, maturation, and trafficking of the γ-secretase complex in alzheimer’s disease. Curr. Alzheimer Res. 2008, 5, 132–146. [Google Scholar] [CrossRef] [PubMed]
- Allinson, T.M.; Parkin, E.T.; Condon, T.P.; Schwager, S.L.; Sturrock, E.D.; Turner, A.J.; Hooper, N.M. The role of ADAM10 and ADAM17 in the ectodomain shedding of angiotensin converting enzyme and the amyloid precursor protein. Eur. J. Biochem. 2004, 271, 2539–2547. [Google Scholar] [CrossRef] [PubMed]
- Zhang, D.; Li, M.; Dong, Y.; Zhang, X.; Liu, X.; Chen, Z.; Zhu, Y.; Wang, H.; Liu, X.; Zhu, J.; et al. 1α, 25-dihydroxyvitamin D3 up-regulates Il-34 expression in SH-SY5Y neural cells. Innate Immun. 2017, 23, 584–591. [Google Scholar] [CrossRef] [PubMed]
- Smith, P.K.; Krohn, R.I.; Hermanson, G.T.; Mallia, A.K.; Gartner, F.H.; Provenzano, M.D.; Fujimoto, E.K.; Goeke, N.M.; Olson, B.J.; Klenk, D.C. Measurement of protein using bicinchoninic acid. Anal. Biochem. 1985, 150, 76–85. [Google Scholar] [CrossRef]
- Grimm, M.O.; Stahlmann, C.P.; Mett, J.; Haupenthal, V.J.; Zimmer, V.C.; Lehmann, J.; Hundsdorfer, B.; Endres, K.; Grimm, H.S.; Hartmann, T. Vitamin E: Curse or benefit in alzheimer’s disease? A systematic investigation of the impact of α-, γ- and δ-tocopherol on ass generation and degradation in neuroblastoma cells. J. Nutr. Health Aging 2015, 19, 646–656. [Google Scholar] [CrossRef] [PubMed]
- Grimm, M.O.; Haupenthal, V.J.; Rothhaar, T.L.; Zimmer, V.C.; Grosgen, S.; Hundsdorfer, B.; Lehmann, J.; Grimm, H.S.; Hartmann, T. Effect of different phospholipids on α-secretase activity in the non-amyloidogenic pathway of alzheimer’s disease. Int. J. Mol. Sci. 2013, 14, 5879–5898. [Google Scholar] [CrossRef] [PubMed]
- Miners, J.S.; Verbeek, M.M.; Rikkert, M.O.; Kehoe, P.G.; Love, S. Immunocapture-based fluorometric assay for the measurement of neprilysin-specific enzyme activity in brain tissue homogenates and cerebrospinal fluid. J. Neurosci. Methods 2008, 167, 229–236. [Google Scholar] [CrossRef] [PubMed]
Analogues | Statistical Test | WT+ | WT+ | WT+ | WT- | WT- | Deficient+ |
---|---|---|---|---|---|---|---|
WT− | Deficient+ | Deficient− | Deficient+ | Deficient− | Deficient− | ||
calcifediol | t test 1 | 0.028 | 0.000 | 0.000 | 0.005 | 0.000 | 0.026 |
Bonferroni 2 | 0.039 | 0.000 | 0.000 | 0.099 | 0.001 | 0.450 | |
alfacalcidol | t test | 0.050 | 0.000 | 0.000 | 0.003 | 0.000 | 0.144 |
Bonferroni | 0.239 | 0.000 | 0.000 | 0.010 | 0.000 | 0.878 | |
calcipotriol | t test | 0.858 | 0.002 | 0.002 | 0.000 | 0.000 | 0.964 |
Bonferroni | 1.000 | 0.001 | 0.001 | 0.002 | 0.002 | 1.000 | |
doxercalciferol | t test | 0.573 | 0.499 | 0.014 | 0.145 | 0.000 | 0.040 |
Bonferroni | 1.000 | 1.000 | 0.038 | 0.873 | 0.005 | 0.226 | |
maxacalcitol | t test | 0.015 | 0.000 | 0.000 | 0.001 | 0.000 | 0.606 |
Bonferroni | 0.167 | 0.000 | 0.000 | 0.001 | 0.000 | 1.000 | |
paricalcitol | t test | 0.179 | 0.000 | 0.000 | 0.000 | 0.000 | 0.223 |
Bonferroni | 0.945 | 0.000 | 0.000 | 0.000 | 0.000 | 1.000 |
Analogues | WT | Deficient | |
---|---|---|---|
calcifediol | alfacalcidol | 1.000 | 1.000 |
calcipotriol | 0.466 | 0.967 | |
doxercalciferol | 0.066 | 1.000 | |
maxacalcitol | 1.000 | 1.000 | |
paricalcitol | 1.000 | 1.000 | |
alfacalcidol | calcipotriol | 1.000 | 1.000 |
doxercalciferol | 0.515 | 1.000 | |
maxacalcitol | 1.000 | 1.000 | |
paricalcitol | 1.000 | 1.000 | |
calcipotriol | doxercalciferol | 1.000 | 0.158 |
maxacalcitol | 1.000 | 1.000 | |
paricalcitol | 1.000 | 1.000 | |
doxercalciferol | maxacalcitol | 0.316 | 0.686 |
paricalcitol | 1.000 | 1.000 | |
maxacalcitol | paricalcitol | 1.000 | 1.000 |
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Grimm, M.O.W.; Thiel, A.; Lauer, A.A.; Winkler, J.; Lehmann, J.; Regner, L.; Nelke, C.; Janitschke, D.; Benoist, C.; Streidenberger, O.; et al. Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation. Int. J. Mol. Sci. 2017, 18, 2764. https://doi.org/10.3390/ijms18122764
Grimm MOW, Thiel A, Lauer AA, Winkler J, Lehmann J, Regner L, Nelke C, Janitschke D, Benoist C, Streidenberger O, et al. Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation. International Journal of Molecular Sciences. 2017; 18(12):2764. https://doi.org/10.3390/ijms18122764
Chicago/Turabian StyleGrimm, Marcus O. W., Andrea Thiel, Anna A. Lauer, Jakob Winkler, Johannes Lehmann, Liesa Regner, Christopher Nelke, Daniel Janitschke, Céline Benoist, Olga Streidenberger, and et al. 2017. "Vitamin D and Its Analogues Decrease Amyloid-β (Aβ) Formation and Increase Aβ-Degradation" International Journal of Molecular Sciences 18, no. 12: 2764. https://doi.org/10.3390/ijms18122764