International Journal of Pharma and Bio Sciences
 
 
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REVIEW ARTICLE
Int J Pharm Bio Sci Volume 12 Issue 1, 2021 (January-March), Pages:65-71

Genetic Regulation of Neural Tube Defects: A Contemporary Review.

Somenath Ghosh
DOI: http://dx.doi.org/10.22376/ijpbs.2021.12.1.b65-71
Abstract:

Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to close completely. It results from failure of the morphogenetic process of neural tube closure (see sidebar). In higher vertebrates, the neural tube is generated by the processes that shape, bend, and fuse the neural plate, and fusion in the dorsal midline progressively seals the neural tube as it forms. If closure is not completed, the neuroepithelium remains exposed to the environment and consequently subject to degeneration and neuronal deficit. Although the unifying feature of open NTDs is incomplete neural tube closure, evidence points to many different possible causes, both genetic and environmental. In humans, it appears that most NTDs are multifactorial, resulting from an additive contribution of several risk factors, which are each individually insufficient to disrupt neural tube closure (the multifactorial threshold model). The type and severity of these open NTDs vary with the level of the body axis affected. Thus, failure of closure in the prospective brain and spinal cord results in anencephaly and open spina bifida (myelomeningocele), respectively. Human NTDs are multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet well understood, but several nongenetic risk factors have been identified as having possibilities for prevention by maternal folic acid supplementation. Mechanisms underlying neural tube closure and NTDs may be informed by experimental models, which have revealed numerous genes whose abnormal function causes NTDs and have provided details of cellular and morphological events whose regulation is essential for closure. Such models also provide an opportunity to investigate potential risk factors and to develop novel preventive therapies

Keywords: Differential expression, Embryogenesis, Factors, Genes, Neurulation, Neural Tube Disorder.
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REFERENCE

1.       Hibbard BM. The role of folic acid in pregnancy; with particular reference to anaemia, abruption and abortion. J Obstet Gynaecol Br Commonw. 1964;71:529-42. doi: 10.1111/j.1471-0528.1964.tb04317.x, PMID 14194440.

2.       Hibbard BM. Defective folate metabolism in pathological conditions of pregnancy. Acta Obstet Gynecol Scand. 1967;46(S7);Suppl 7:47-59. doi: 10.3109/00016346709157073, PMID 6072974.

3.       Smithells RW, Sheppard S, Schorah CJ. Vitamin deficiencies and neural tube defects. Arch Dis Child. 1976;51(12):944-50. doi: 10.1136/adc.51.12.944, PMID 1015847.

4.       Steegers-Theunissen RP, Boers GH, Trijbels FJ, Eskes TK. Neural-tube defects and derangement of homocysteine metabolism. N Engl J Med. 1991;324(3):199-200. doi: 10.1056/NEJM199101173240315, PMID 1984202.

5.       Mills JL, McPartlin JM, Kirke PN, Lee YJ, Conley MR, Weir DG, Scott JM. Homocysteine metabolism in pregnancies complicated by neural-tube defects. Lancet. 1995;345(8943):149-51. doi: 10.1016/s0140-6736(95)90165-5, PMID 7741859.

6.       Nasri K, Ben-Fradj MK, Touati A, Aloui M, Ben-Jemaa N, Masmoudi A, Elmay MV, Omar S, Feki M, Kaabechi N, Marrakchi R, Gaigi SS. Association of maternal homocysteine and vitamins status with the risk of neural tube defects in Tunisia: A case-control study. Birth Defects Res A Clin Mol Teratol. 2015;103(12):1011-20. doi: 10.1002/bdra.23418, PMID 26386249.

7.       Castilla EE, Orioli IM, Lopez-Camelo JS, Dutra Mda G, Nazer-Herrera J, Latin American Collaborative Study of Congenital Malformations (ECLAMC). Preliminary data on changes in neural tube defect prevalence rates after folic acid fortification in South America. Am J Med Genet A. 2003;123A(2):123-8. doi: 10.1002/ajmg.a.20230, PMID 14598335.

8.       Mills JL, Signore C. Neural tube defect rates before and after food fortification with folic acid. Birth Defects Res A. 2004;70(11):844-5. doi: 10.1002/bdra.20075, PMID 15468072.

9.       Sayed AR, Bourne D, Pattinson R, Nixon J, Henderson B. Decline in the prevalence of neural tube defects following folic acid fortification and its cost–benefit in South Africa. Birth Defects Res A Clin Mol Teratol. 2008;82(4):211-6. doi: 10.1002/bdra.20442, PMID 18338391.

10.     Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet. 1991;338(8760):131-7. PMID 1677062.

11.     Singh K, Rai SK, Pandey S, Kumari P, Sharma V, Prasad, Pandey BL, Srivastava A, Rashmi, Shamal S, Singh R. Folate deficiency is not the only cause of neural tube defects: A Preliminary Study. Ind J Prev Soc Med. 2016;47, 192-97. ISSN No:0301-1216.

12.     Elwood JM, Little J, Elwood JH. Epidemiology and control of neural tube defects: monographs in epidemiology and biostatistics. Oxford: Oxford University Press; 1992.

13.     Volcik KA, Blanton SH, Kruzel MC, Townsend IT, Tyerman GH, Mier RJ, Northrup H. Testing for genetic associations with the PAX gene family in a spina bifida population. Am J Med Genet. 2002;110(3):195-202. doi: 10.1002/ajmg.10434, PMID 12116225.

14.     Barber RC, Lammer EJ, Shaw GM, Greer KA, Finnell RH. The role of folate transport and metabolism in neural tube defect risk. Mol Genet Metab. 1999;66(1):1-9. doi: 10.1006/mgme.1998.2787, PMID 9973541.

15.     Amorim MR, Lima MA, Castilla EE, Orioli IM. Non-Latin European descent could be a requirement for association of NTDs and MTHFR variant 677C > T: a meta-analysis. Am J Med Genet A. 2007;143A(15):1726-32. doi: 10.1002/ajmg.a.31812, PMID 17618486.

16.     Etheredge AJ, Finnell RH, Carmichael SL, Lammer EJ, Zhu H, Mitchell LE, Shaw GM. Maternal and infant gene-folate interactions and the risk of neural tube defects. Am J Med Genet A. 2012;158A(10):2439-46. doi: 10.1002/ajmg.a.35552, PMID 22903727.

17.     Momb J, Appling DR. Mitochondrial one-carbon metabolism and neural tube defects. Birth Defects Res A Clin Mol Teratol. 2014;100(8):576-83. doi: 10.1002/bdra.23268, PMID 24985542.

18.     Copp AJ, Stanier P, Greene ND. Neural tube defects: recent advances, unsolved questions, and controversies. Lancet Neurol. 2013;12(8):799-810. doi: 10.1016/S1474-4422(13)70110-8, PMID 23790957.

19.     Molloy AM, Kirke P, Hillary I, Weir DG, Scott JM. Maternal serum folate and vitamin B12 concentrations in pregnancies associated with neural tube defects. Arch Dis Child. 1985;60(7):660-5. doi: 10.1136/adc.60.7.660, PMID 4026363.

20.     Mills JL, Tuomilehto J, Yu KF, Colman N, Blaner WS, Koskela P, Rundle WE, Forman M, Toivanen L, Rhoads GG. Maternal vitamin levels during pregnancies producing infants with neural tube defects. J Pediatr. 1992;120(6):863-71. doi: 10.1016/S0022-3476(05)81951-1, PMID 1593344.

21.     Kirke PN, Molloy AM, Daly LE, Burke H, Weir DG, Scott JM. Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects. Q J Med. 1993;86(11):703-8. PMID 8265769.

22.     Suh JR, Herbig AK, Stover PJ. New perspectives on folate catabolism. Annu Rev Nutr. 2001;21:255-82. doi: 10.1146/annurev.nutr.21.1.255, PMID 11375437.

23.     Schirch V, Strong WB. Interaction of folylpolyglutamates with enzymes in one-carbon metabolism. Arch Biochem Biophys. 1989;269(2):371-80. doi: 10.1016/0003-9861(89)90120-3, PMID 2645826.

24.     Appling DR. Compartmentation of folate-mediated one-carbon metabolism in eukaryotes. FASEB J. 1991;5(12):2645-51. doi: 10.1096/fasebj.5.12.1916088, PMID 1916088.

25.     Wagner C. BIOCHEMICAL ROLE OF FOLATE IN CELLULAR METABOLISM. Clinical Research and Regulatory Affairs. 2001;18(3):161-80. doi: 10.1081/CRP-100108171.

26.     Crider KS, Devine O, Hao L, Dowling NF, Li S, Molloy AM, Li Z, Zhu J, Berry RJ. Population red blood cell folate concentrations for prevention of neural tube defects: bayesian model. BMJ. 2014;349:g4554. doi: 10.1136/bmj.g4554, PMID 25073783.

27.     Blom HJ, Shaw GM, den Heijer M, Finnell RH. Neural tube defects and folate: case far from closed. Nat Rev Neurosci. 2006;7(9):724-31. doi: 10.1038/nrn1986, PMID 16924261.

28.     Zhao R, Diop-Bove N, Visentin M, Goldman ID. Mechanisms of membrane transport of folates into cells and across epithelia. Annu Rev Nutr. 2011;31:177-201. doi: 10.1146/annurev-nutr-072610-145133, PMID 21568705.

29.     Bailey LB, Stover PJ, McNulty H, Fenech MF, Gregory JF 3rd, Mills JL, Pfeiffer CM, Fazili Z, Zhang M, Ueland PM, Molloy AM, Caudill MA, Shane B, Berry RJ, Bailey RL, Hausman DB, Raghavan R, Raiten DJ. Biomarkers of nutrition for development-folate review. J Nutr. 2015;145(7):1636S-80S. doi: 10.3945/jn.114.206599, PMID 26451605.

30.     Shane B. Folate chemistry and metabolism. In: Bailey LP, editor, Folate in health and disease. Marcel Dekkar, New York. ISBN No. 9781420071245; 1995. p. 23-42.

31.     Beaudin AE, Stover PJ. Insights into metabolic mechanisms underlying folate-responsive neural tube defects: a minireview. Birth Defects Res A Clin Mol Teratol. 2009;85(4):274-84. doi: 10.1002/bdra.20553, PMID 19180567.

32.     Scotti M, Stella L, Shearer EJ, Stover PJ. Modeling cellular compartmentation in one-carbon metabolism. Wiley Interdiscip Rev Syst Biol Med. 2013;5(3):343-65. doi: 10.1002/wsbm.1209. PMID 23408533.

33.     Wang YC, Chiang EPI. Low-dose methotrexate Inhibits methionine S-adenosyl transferase in vitro and in vivo. Mol Med. 2012;18:423-32. doi: 10.2119/molmed.2011.00048, PMID 22193356.

34.     Shane B. Folylpolyglutamate synthesis and role in the regulation of one-carbon metabolism. Vitam Horm. 1989;45:263-335. doi: 10.1016/s0083-6729(08)60397-0, PMID 2688305.

35.     Anderson DD, Woeller CF, Stover PJ. Small ubiquitin-like modifier-1 (SUMO-1) modification of thymidylate synthase and dihydrofolatereductase. Clin Chem Lab Med. 2007;45(12):1760-63. doi: 10.1515/CCLM.2007.355, PMID 18067453.

36.     Woeller CF, Anderson DD, Szebenyi DM, Stover PJ. Evidence for small ubiquitin-like modifier-dependent nuclear import of the thymidylate biosynthesis pathway. J Biol Chem. 2007;282(24):17623-31. doi: 10.1074/jbc.M702526200, PMID 17446168.

37.     Bailey LB. Folate requirements and dietary recommendations. In: Bailey LP, editor, Folate in health and disease. Marcel Dekkar, New York. ISBN No. 9781420071245; 1995. p. 123-52.

38.     Stover PJ, Garza C. Bringing individuality to public health recommendations. J Nutr. 2002;132(8);Suppl:2476S-80S. https://doi:10.1093/jn/132.8.2476S. doi: 10.1093/jn/132.8.2476S, PMID 12163715.

39.     Stover PJ. Physiology of folate and vitamin B12 in health and disease. Nutr Rev. 2004;62(6 Pt 2):S3-12; discussion S13. doi: 10.1111/j.1753-4887.2004.tb00070.x, PMID 15298442.

40.     Blount BC, Mack MM, Wehr CM, MacGregor JT, Hiatt RA, Wang G, Wickramasinghe SN, Everson RB, Ames BN. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc Natl Acad Sci U S A. 1997;94(7):3290-5. doi: 10.1073/pnas.94.7.3290, PMID 9096386.

41.     Selhub J. Homocysteine metabolism. Annu Rev Nutr. 1999;19:217-46. doi: 10.1146/annurev.nutr.19.1.217, PMID 10448523.

42.     Rampersaud E, Melvin EC, Siegel D, Mehltretter L, Dickerson ME, George TM, Enterline D, Nye JS, Speer MC, NTD Collaborative Group. Updated investigations of the role of methylenetetrahydrofolate reductase in human neural tube defects. Clin Genet. 2003;63(3):210-4. doi: 10.1034/j.1399-0004.2003.00043.x, PMID 12694231.

43.     Bai S, Ghoshal K, Datta J, Majumder S, Yoon SO, Jacob ST. DNA methyltransferase 3b regulates nerve growth factor-induced differentiation of PC12 cells by recruiting histone deacetylase 2. Mol Cell Biol. 2005;25(2):751-66. doi: 10.1128/MCB.25.2.751-766.2005, PMID 15632075.

44.     Gregory JF. 3rd case study: folate bioavailability. J Nutr. 2001;131(4);Suppl:1376S-82S. doi: 10.1093/jn/131.4.1376S, PMID 11285357.

45.     Tamura T, Stokstad EL. The availability of food folate in man. Br J Haematol. 1973;25(4):513-32. doi: 10.1111/j.1365-2141.1973.tb01763.x, PMID 4201754.

46.     Qiu A, Jansen M, Sakaris A, Min SH, Chattopadhyay S, Tsai E, Sandoval C, Zhao R, Akabas MH, Goldman ID. Identification of an intestinal folate transporter and the molecular basis for hereditary folate mal-absorption. Cell. 2006;127(5):917-28. doi: 10.1016/j.cell.2006.09.041, PMID 17129779.

47.     Ifergan I, Jansen G, Assaraf YG. The reduced folate carrier (RFC) is cytotoxic to cells under conditions of severe folate deprivation. RFC as a double edged sword in folate homeostasis. J Biol Chem. 2008;283(30):20687-95. doi: 10.1074/jbc.M802812200, PMID 18499665.

48.     Kamen BA, Wang MT, Streckfuss AJ, Peryea X, Anderson RG. Delivery of folates to the cytoplasm of MA104 cells is mediated by a surface membrane receptor that recycles. J Biol Chem. 1988;263(27):13602-9. doi: 10.1016/S0021-9258(18)68284-5, PMID 3417674.

49.     Yang N, Wang L, Finnell RH, Li Z, Jin L, Zhang L, Cabrera RM, Ye R, Ren A. Levels of folate receptor autoantibodies in maternal and cord blood and risk of neural tube defects in a Chinese population. Birth Def Res Clin Mol Teratol. 2016;106(8):685-95. doi: 10.1002/bdra.23517, PMID 27166990.

50.     Barber RC, Shaw GM, Lammer EJ, Greer KA, Biela TA, Lacey SW, Wasserman CR, Finnell RH. Lack of association between mutations in the folate receptor-alpha gene and spina bifida. Am J Med Genet. 1998;76(4):310-7. doi: 10.1002/(SICI)1096-8628(19980401)76:4<310::AID-AJMG6>3.0.CO;2-T, PMID 9545095.

51.     O’Leary VB, Mills JL, Kirke PN, Parle-McDermott A, Swanson DA, Weiler A, Pangilinan F, Conley M, Molloy AM, Lynch M, Cox C, Scott JM, Brody LC. Analysis of the human folate receptor beta gene for an association with neural tube defects. Mol Genet Metab. 2003;79(2):129-33. doi: 10.1016/s1096-7192(03)00075-1, PMID 12809644.

52.     Boyles AL, Billups AV, Deak KL, Siegel DG, Mehltretter L, Slifer SH, Bassuk AG, Kessler JA, Reed MC, Nijhout HF, George TM, Enterline DS, Gilbert JR, Speer MC, NTD Collaborative Group. Neural tube defects and folate pathway genes:family-based association tests of gene-gene and gene-environment interactions. Environ Health Perspect. 2006;114(10):1547-52. doi: 10.1289/ehp.9166, PMID 17035141.

53.     Watanabe M, Osada J, Aratani Y, Kluckman K, Reddick R, Malinow MR, Maeda N. Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia. Proc Natl Acad Sci U S A. 1995;92(5):1585-9. doi: 10.1073/pnas.92.5.1585, PMID 7878023.

54.     Shaw GM, Lammer EJ, Zhu H, Baker MW, Neri E, Finnell RH. Maternal periconceptional vitamin use, genetic variation of infant reduced folate carrier (A80G), and risk of spina bifida. Am J Med Genet. 2002;108(1):1-6. doi: 10.1002/ajmg.10195, PMID 11857541.

55.     Morin I, Devlin AM, Leclerc D, Sabbaghian N, Halsted CH, Finnell R, Rozen R. Evaluation of genetic variants in the reduced folate carrier and in glutamate carboxypeptidase II for spina bifida risk. Mol Genet Metab. 2003;79(3):197-200. doi: 10.1016/s1096-7192(03)00086-6, PMID 12855225.

56.     Pei L, Zhu H, Ren A, Li Z, Hao L, Finnell RH, Li Z. Reduced folate carrier gene is a risk factor for neural tube defects in a Chinese population. Birth Def Res Clin Mol Teratol. 2005;73(6):430-3. doi: 10.1002/bdra.20130, PMID 15799025.

57.     Afman LA, Trijbels FJ, Blom HJ. The H475Y polymorphism in the glutamate carboxypeptidase II gene increases plasma folate without affecting the risk for neural tube defects in humans. J Nutr. 2003;133(1):75-7. doi: 10.1093/jn/133.1.75, PMID 12514270.

58.     Mohanty V, Shah A, Allender E, Siddiqui MR, Monick S, Ichi S, Mania-Farnell BG, G McLone D, Tomita T, Mayanil CS. Folate Receptor alpha Upregulates Oct4, Sox2 and Klf4 and Downregulates miR-138 and miR-let-7 in Cranial Neural Crest Cells. Stem Cells. 2016;34(11):2721-32. doi: 10.1002/stem.2421, PMID 27300003.

59.     Balashova OA, OlesyaVisina O, Borodinsky L. Wiley periodicals Inc. Dev Neurobiol. 2018;78:391-402. doi: 10.1002/dneu.22579.

60.     Piedrahita JA, Oetama B, Bennett GD, van Waes J, Kamen BA, Richardson J, Lacey SW, Anderson RG, Finnell RH. Mice lacking the folic acid-binding protein Folbp1 are defective in early embryonic development. Nat Genet. 1999;23(2):228-32. doi: 10.1038/13861, PMID 10508523.

61.     Finnell RH, Spiegelstein O, Wlodarczyk B, Triplett A, Pogribny IP, Melnyk S, James JS. DNA methylation in Folbp1 knockout mice supplemented with folic acid during gestation. J Nutr. 2002;132(8);Suppl:2457S-61S. doi: 10.1093/jn/132.8.2457S, PMID 12163711.

62.     Zhao R, Russell RG, Wang Y, Liu L, Gao F, Kneitz B, Edelmann W, Goldman ID. Rescue of embryonic lethality in reduced folate carrier-deficient mice by maternal folic acid supplementation reveals early neonatal failure of hematopoietic organs. J Biol Chem. 2001;276(13):10224-8. doi: 10.1074/jbc.c000905200, PMID 11266438.

63.     Pietrzik K, Bailey L, Shane B. Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2010;49(8):535-48. doi: 10.2165/11532990-000000000-00000, PMID 20608755.

64.     Christensen KE, MacKenzie RE. Mitochondrial one-carbon metabolism is adapted to the specific needs of yeast, plants and mammals. BioEssays. 2006;28(6):595-605. doi: 10.1002/bies.20420, PMID 16700064.

65.     Motokawa Y, Kikuchi G. Glycine metabolism in rat liver mitochondria. V. Intramitochondrial localization of the reversible glycine cleavage system and serine hydroxymethyltransferase. Arch Biochem Biophys. 1971;146(2):461-64. doi: 10.1016/0003-9861(71)90149-4, PMID 4107181.

66.     Wittwer AJ, Wagner C. Identification of the folate-binding proteins of rat liver mitochondria as dimethylglycine dehydrogenase and sarcosine dehydrogenase. Purification and folate-binding characteristics. J Biol Chem. 1981;256(8):4102-8. doi: 10.1016/S0021-9258(19)69571-2, PMID 6163777.

67.     Christensen KE, Patel H, Kuzmanov U, Narciso RM, MacKenzie RE. Disruption of the mthfd1 gene reveals a monofunctional 10-formyltetrahydrofolate synthetase in mammalian mitochondria. J Biol Chem. 2005;280:7597-602. doi: 10.1074/jbc.M409380200.

68.     Imbard A, Benoist JF, Blom HJ. Neural tube defects, folic acid and methylation. Int J Environ Res Public Health. 2013;10(9):4352-89. doi: 10.3390/ijerph10094352, PMID 24048206. Int. J. Env. Imbard A, Benoist JF, Blom HJ. Neural tube defects, folic acid and methylation. Health. 2013;10(9):4352-89. doi: 10.3390/ijerph10094352, PMID 24048206.

69.     Crider KS, Qi YP, Devine O, Tinker SC, Berry RJ. Modeling the impact of folic acid fortification and supplementation on red blood cell folate concentrations and predicted neural tube defect risk in the United States: have we reached optimal prevention? Am J Clin Nutr. 2018;107(6):1027-34. doi: 10.1093/ajcn/nqy065, PMID 29767673.

70.     Salih MA, Murshid WR, Seidahmed MZ. Epidemiology, prenatal management, and prevention of neural tube defects. Saudi Med J. 2014;35;Suppl 1:S15-28. PMID 25551106.

71.     Wallingford JB. Neural tube closure and neural tube defects: studies in animal models reveal known knowns and known unknowns. Am J Med Genet C. 2005;135C(1):59-68. doi: 10.1002/ajmg.c.30054, PMID 15806594.

72.     Taparia S, Gelineau-van Waes J, Rosenquist TH, Finnell RH. Importance of folate-homocysteine homeostasis during early embryonic development. Clin Chem Lab Med. 2007;45(12):1717-27. doi: 10.1515/CCLM.2007.345, PMID 18067451.

73.     MacFarlane AJ, Liu X, Perry CA, Flodby P, Allen RH, Stabler SP, Stover PJ. Cytoplasmic serine hydroxymethyltransferase regulates the metabolic partitioning of methylenetetrahydrofolate but is not essential in mice. J Biol Chem. 2008;283(38):25846-53. doi: 10.1074/jbc.M802671200, PMID 18644786.

74.     Beaudin AE, Stover PJ. Folate-mediated one-carbon metabolism and neural tube defects: balancing genome synthesis and gene expression. Birth Defects Res C Embryo Today. Today. 2007;81(3):183-203. doi: 10.1002/bdrc.20100, PMID 17963270.

75.     Stover PJ. One-carbon metabolism–genome interactions in folate-associated pathologies. J Nutr. 2009;139(12):2402-5. doi: 10.3945/jn.109.113670, PMID 19812215.

76.     Leduc D, Graziani S, Meslet-Cladiere L, Sodolescu A, Liebl U, Myllykallio H. Two distinct pathways for thymidylate (dTMP) synthesis in (hyper) thermophilic Bacteria and Archaea. Biochem Soc Trans. 2004;32(2):231-5. doi: 10.1042/bst0320231, PMID 15046578.

77.     Avendaño C, Menéndez JC. Medicinal chemistry of anticancer drugs. 2nd ed. The Netherlands: Elsevier. ISBN No. 9780444626677; 2008.

78.     Scott JM, Dinn JJ, Wilson P, Weir DG. Pathogenesis of subacute combined degeneration: a result of methyl group deficiency. Lancet. 1981;2(8242):334-7. doi: 10.1016/s0140-6736(81)90649-8, PMID 6115112.

79.     Green JM, MacKenzie RE, Matthews RG. Substrate flux through methylenetetrahydrofolate dehydrogenase: predicted effects of the concentration of methylenetetrahydrofolate on its partitioning into pathways leading to nucleotide biosynthesis or methionine regeneration. Biochemistry. 1988;27(21):8014-22. doi: 10.1021/bi00421a007, PMID 3266075.

80.     Rijnboutt S, Jansen G, Posthuma G, Hynes JB, Schornagel JH, Strous GJ. Endocytosis of GPI-linked membrane folate receptor-alpha. J Cell Biol. 1996;132(1-2):35-47. doi: 10.1083/jcb.132.1.35, PMID 8567728.

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