{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:39:26Z","timestamp":1791207566158,"version":"4.1.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2016,4,30]],"date-time":"2016-04-30T00:00:00Z","timestamp":1461974400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Neurosci"],"published-print":{"date-parts":[[2016,7]]},"DOI":"10.1007\/s12031-016-0760-5","type":"journal-article","created":{"date-parts":[[2016,4,30]],"date-time":"2016-04-30T02:12:20Z","timestamp":1461982340000},"page":"382-391","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Tocotrienol Treatment in Familial Dysautonomia: Open-Label Pilot Study"],"prefix":"10.1007","volume":"59","author":[{"given":"David","family":"Cheishvili","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Channa","family":"Maayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naama","family":"Holzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanna","family":"Tsenter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elad","family":"Lax","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Petropoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aharon","family":"Razin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,4,30]]},"reference":[{"issue":"5","key":"760_CR1","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1002\/humu.1117","volume":"17","author":"J Alonso","year":"2001","unstructured":"Alonso J, Garcia-Miguel P, Abelairas J, Mendiola M, Sarret E, Vendrell MT, et al. (2001) Spectrum of germline RB1 gene mutations in Spanish retinoblastoma patients: phenotypic and molecular epidemiological implications. Human Mutat 17(5):412\u2013422","journal-title":"Human Mutat"},{"issue":"3","key":"760_CR2","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1086\/318808","volume":"68","author":"SL Anderson","year":"2001","unstructured":"Anderson SL, Coli R, Daly IW, Kichula EA, Rork MJ, Volpi SA, et al. (2001) Familial dysautonomia is caused by mutations of the IKAP gene. Am J Hum Genet 68(3):753\u2013758","journal-title":"Am J Hum Genet"},{"issue":"2","key":"760_CR3","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.bbrc.2003.09.019","volume":"310","author":"SL Anderson","year":"2003","unstructured":"Anderson SL, Qiu J, Rubin BY (2003a) EGCG corrects aberrant splicing of IKAP mRNA in cells from patients with familial dysautonomia. Biochem Biophys Res Commun 310(2):627\u2013633","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"760_CR4","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0006-291X(03)00971-9","volume":"306","author":"SL Anderson","year":"2003","unstructured":"Anderson SL, Qiu J, Rubin BY (2003b) Tocotrienols induce IKBKAP expression: a possible therapy for familial dysautonomia. Biochem Biophys Res Commun 306(1):303\u2013309","journal-title":"Biochem Biophys Res Commun"},{"issue":"24","key":"760_CR5","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1093\/hmg\/10.24.2841","volume":"10","author":"C Andreassi","year":"2001","unstructured":"Andreassi C, Jarecki J, Zhou J, Coovert DD, Monani UR, Chen X, et al. (2001) Aclarubicin treatment restores SMN levels to cells derived from type I spinal muscular atrophy patients. Human Mol Genet 10(24):2841\u20132849","journal-title":"Human Mol Genet"},{"issue":"Suppl 1","key":"760_CR6","doi-asserted-by":"crossref","first-page":"I2","DOI":"10.1007\/s102860200014","volume":"12","author":"FB Axelrod","year":"2002","unstructured":"Axelrod FB (2002) Hereditary sensory and autonomic neuropathies. Familial dysautonomia and other HSANs. Clinical autonomic research. Off J Clin Auton Res Soc 12(Suppl 1):I2\u201314.","journal-title":"Off J Clin Auton Res Soc"},{"issue":"3","key":"760_CR7","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1002\/mus.10499","volume":"29","author":"FB Axelrod","year":"2004","unstructured":"Axelrod FB (2004) Familial dysautonomia. Muscle Nerve 29(3):352\u2013363","journal-title":"Muscle Nerve"},{"issue":"4","key":"760_CR8","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1517\/14656566.6.4.561","volume":"6","author":"FB Axelrod","year":"2005","unstructured":"Axelrod FB (2005) Familial dysautonomia: a review of the current pharmacological treatments. Expert opin Pharmacother 6(4):561\u2013567","journal-title":"Expert opin Pharmacother"},{"key":"760_CR9","unstructured":"Axelrod FB, Maayan CH (1999) Familial Dysautonomia.\u00a0In Gellis and Kagen's current pediatric therapy, 16th ed., eds. F. D. Burg, J. R. Ingelfinger, E. R. Wald, and R. A. Polin, 466-469. Philadelphia: WB Saunders"},{"issue":"1","key":"760_CR10","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/1098-1004(2001)17:1<75::AID-HUMU16>3.0.CO;2-6","volume":"17","author":"GW Birrell","year":"2001","unstructured":"Birrell GW, Ramsay JR, Tung JJ, Lavin MF (2001) Exon skipping in the ATM gene in normal individuals: the effect of blood sample storage on RT-PCR analysis. Human Mutat 17(1):75\u201376","journal-title":"Human Mutat"},{"issue":"7","key":"760_CR11","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/sj.ejcn.1601186","volume":"55","author":"KJ Blades","year":"2001","unstructured":"Blades KJ, Patel S, Aidoo KE (2001) Oral antioxidant therapy for marginal dry eye. Eur J Clin Nutri 55(7):589\u2013597","journal-title":"Eur J Clin Nutri"},{"issue":"14","key":"760_CR12","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1093\/hmg\/ddt126","volume":"22","author":"R Bochner","year":"2013","unstructured":"Bochner R, Ziv Y, Zeevi D, Donyo M, Abraham L, Ashery-Padan R, et al. (2013) Phosphatidylserine increases IKBKAP levels in a humanized knock-in IKBKAP mouse model. Human Mol Genet 22(14):2785\u20132794","journal-title":"Human Mol Genet"},{"issue":"17","key":"760_CR13","doi-asserted-by":"crossref","first-page":"9808","DOI":"10.1073\/pnas.171105098","volume":"98","author":"JG Chang","year":"2001","unstructured":"Chang JG, Hsieh-Li HM, Jong YJ, Wang NM, Tsai CH, Li H (2001) Treatment of spinal muscular atrophy by sodium butyrate. Proceed Natl Acad Sci USA 98(17):9808\u20139813","journal-title":"Proceed Natl Acad Sci USA"},{"issue":"17","key":"760_CR14","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1093\/hmg\/ddm157","volume":"16","author":"D Cheishvili","year":"2007","unstructured":"Cheishvili D, Maayan C, Smith Y, Ast G, Razin A (2007) IKAP\/hELP1 deficiency in the cerebrum of familial dysautonomia patients results in down regulation of genes involved in oligodendrocyte differentiation and in myelination. Hum Mol Genet 16(17):2097\u20132104","journal-title":"Hum Mol Genet"},{"key":"760_CR15","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.autneu.2013.10.009","volume":"180","author":"D Cheishvili","year":"2014","unstructured":"Cheishvili D, Laiba E, Rekhtman D, Claman A, Razin A, Maayan C (2014) Dynamic changes in IKBKAP mRNA levels during crisis of familial dysautonomia patients. Auton Neurosci Basic Clin 180:59\u201365","journal-title":"Auton Neurosci Basic Clin"},{"issue":"3","key":"760_CR16","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1097\/ALN.0b013e318267084d","volume":"117","author":"SD Cook-Sather","year":"2012","unstructured":"Cook-Sather SD, Viola L, Zur KB, Rubin BY (2012) Case scenario: perioperative administration of tocotrienols and green tea extract in a child with familial dysautonomia. Anesthesiology 117(3):639\u2013645","journal-title":"Anesthesiology"},{"issue":"3","key":"760_CR17","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1086\/368263","volume":"72","author":"MP Cuajungco","year":"2003","unstructured":"Cuajungco MP, Leyne M, Mull J, Gill SP, Lu W, Zagzag D, et al. (2003) Tissue-specific reduction in splicing efficiency of IKBKAP due to the major mutation associated with familial dysautonomia. Am J Human genet 72(3):749\u2013758","journal-title":"Am J Human genet"},{"key":"760_CR18","first-page":"711","volume":"8","author":"C Galbis-Estrada","year":"2013","unstructured":"Galbis-Estrada C, Pinazo-Duran MD, Cantu-Dibildox J, Marco-Ramirez C, Diaz-Llopis M, Benitez-del-Castillo J (2013) Patients undergoing long-term treatment with antihypertensive eye drops responded positively with respect to their ocular surface disorder to oral supplementation with antioxidants and essential fatty acids. Clin Inter Aging 8:711\u2013719","journal-title":"Clin Inter Aging"},{"issue":"3","key":"760_CR19","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1203\/PDR.0b013e318194fd52","volume":"65","author":"G Gold-von Simson","year":"2009","unstructured":"Gold-von Simson G, Goldberg JD, Rolnitzky LM, Mull J, Leyne M, Voustianiouk A, et al. (2009) Kinetin in familial dysautonomia carriers: implications for a new therapeutic strategy targeting mRNA splicing. Pediatric Res 65(3):341\u2013346","journal-title":"Pediatric Res"},{"issue":"6","key":"760_CR20","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1007\/s00439-001-0632-z","volume":"109","author":"CP Guimaraes","year":"2001","unstructured":"Guimaraes CP, Lemos M, Menezes I, Coelho T, Sa-Miranda C, Azevedo JE (2001) Characterisation of two mutations in the ABCD1 gene leading to low levels of normal ALDP. Human Genet 109(6):616\u2013622","journal-title":"Human Genet"},{"issue":"2","key":"760_CR21","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1002\/1096-8628(20010615)101:2<130::AID-AJMG1333>3.0.CO;2-V","volume":"101","author":"D Guo","year":"2001","unstructured":"Guo D, Tan FK, Cantu A, Plon SE, Milewicz DM (2001) FBN1 exon 2 splicing error in a patient with Marfan syndrome. Am J Med Genet 101(2):130\u2013134","journal-title":"Am J Med Genet"},{"issue":"12","key":"760_CR22","doi-asserted-by":"crossref","first-page":"e15884","DOI":"10.1371\/journal.pone.0015884","volume":"5","author":"H Keren","year":"2010","unstructured":"Keren H, Donyo M, Zeevi D, Maayan C, Pupko T, Ast G (2010) Phosphatidylserine increases IKBKAP levels in familial dysautonomia cells. PLoS ONE 5(12):e15884","journal-title":"PLoS ONE"},{"issue":"12","key":"760_CR23","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1373\/clinchem.2003.022681","volume":"49","author":"BL Lee","year":"2003","unstructured":"Lee BL, New AL, Ong CN (2003) Simultaneous determination of tocotrienols, tocopherols, retinol, and major carotenoids in human plasma. Clin Chem 49(12):2056\u20132066","journal-title":"Clin Chem"},{"issue":"5","key":"760_CR24","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1001\/archopht.1956.00930040727011","volume":"56","author":"SD Liebman","year":"1956","unstructured":"Liebman SD (1956) Ocular manifestations of Riley-day syndrome; familial autonomic dysfunction. AMA Arch Ophthalmol 56(5):719\u2013725","journal-title":"AMA Arch Ophthalmol"},{"issue":"2","key":"760_CR25","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1399-0004.1987.tb03334.x","volume":"32","author":"C Maayan","year":"1987","unstructured":"Maayan C, Kaplan E, Shachar S, Peleg O, Godfrey S (1987) Incidence of familial dysautonomia in Israel 1977-1981. Clin Genet 32(2):106\u2013108","journal-title":"Clin Genet"},{"issue":"3","key":"760_CR26","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S0925-4439(00)00072-7","volume":"1502","author":"K Mayer","year":"2000","unstructured":"Mayer K, Ballhausen W, Leistner W, Rott H (2000) Three novel types of splicing aberrations in the tuberous sclerosis TSC2 gene caused by mutations apart from splice consensus sequences. Biochimica et biophysica acta 1502(3):495\u2013507","journal-title":"Biochimica et biophysica acta"},{"issue":"1","key":"760_CR27","doi-asserted-by":"crossref","first-page":"37","DOI":"10.7326\/0003-4819-142-1-200501040-00110","volume":"142","author":"ER Miller 3rd","year":"2005","unstructured":"Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E (2005) Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Internal Med 142(1):37\u201346","journal-title":"Ann Internal Med"},{"issue":"2","key":"760_CR28","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1002\/jnr.21851","volume":"87","author":"K Miyamoto","year":"2009","unstructured":"Miyamoto K, Shiozaki M, Shibata M, Koike M, Uchiyama Y, Gotow T (2009) Very-high-dose alpha-tocopherol supplementation increases blood pressure and causes possible adverse central nervous system effects in stroke-prone spontaneously hypertensive rats. J Neurosci Res 87(2):556\u2013566","journal-title":"J Neurosci Res"},{"issue":"6","key":"760_CR29","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1093\/ajcn\/76.6.1237","volume":"76","author":"VA Mustad","year":"2002","unstructured":"Mustad VA, Smith CA, Ruey PP, Edens NK, DeMichele SJ (2002) Supplementation with 3 compositionally different tocotrienol supplements does not improve cardiovascular disease risk factors in men and women with hypercholesterolemia. Am J Clin Nutri 76(6):1237\u20131243","journal-title":"Am J Clin Nutri"},{"issue":"8","key":"760_CR30","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/S0278-6915(01)00025-4","volume":"39","author":"H Nakamura","year":"2001","unstructured":"Nakamura H, Furukawa F, Nishikawa A, Miyauchi M, Son HY, Imazawa T, et al. (2001) Oral toxicity of a tocotrienol preparation in rats. Food Chem Toxicol Int J Publi Brit Ind Biol Res Assoc 39(8):799\u2013805","journal-title":"Food Chem Toxicol Int J Publi Brit Ind Biol Res Assoc"},{"issue":"3","key":"760_CR31","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0168-9525(01)02619-1","volume":"18","author":"M Nissim-Rafinia","year":"2002","unstructured":"Nissim-Rafinia M, Kerem B (2002) Splicing regulation as a potential genetic modifier. Trends genet TIG 18(3):123\u2013127","journal-title":"Trends genet TIG"},{"issue":"28","key":"760_CR32","doi-asserted-by":"crossref","first-page":"21041","DOI":"10.1074\/jbc.M910165199","volume":"275","author":"F Pagani","year":"2000","unstructured":"Pagani F, Buratti E, Stuani C, Romano M, Zuccato E, Niksic M, et al. (2000) Splicing factors induce cystic fibrosis transmembrane regulator exon 9 skipping through a nonevolutionary conserved intronic element. J Biol Chem 275(28):21041\u201321047","journal-title":"J Biol Chem"},{"issue":"6","key":"760_CR33","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1111\/j.1755-3768.1993.tb08607.x","volume":"71","author":"S Patel","year":"1993","unstructured":"Patel S, Plaskow J, Ferrier C (1993) The influence of vitamins and trace element supplements on the stability of the pre-corneal tear film. Acta Ophthalmol 71(6):825\u2013829","journal-title":"Acta Ophthalmol"},{"issue":"12","key":"760_CR34","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1136\/bjo.86.12.1369","volume":"86","author":"V Peponis","year":"2002","unstructured":"Peponis V, Papathanasiou M, Kapranou A, Magkou C, Tyligada A, Melidonis A, et al. (2002) Protective role of oral antioxidant supplementation in ocular surface of diabetic patients. Brit J Ophthalmol 86(12):1369\u20131373","journal-title":"Brit J Ophthalmol"},{"issue":"5","key":"760_CR35","first-page":"CR213","volume":"10","author":"V Peponis","year":"2004","unstructured":"Peponis V, Bonovas S, Kapranou A, Peponi E, Filioussi K, Magkou C, et al. (2004) Conjunctival and tear film changes after vitamin C and E administration in non-insulin dependent diabetes mellitus. Med Sci Monitor Int Med J Exp Clin Res 10(5):CR213\u2013CR217","journal-title":"Med Sci Monitor Int Med J Exp Clin Res"},{"issue":"9","key":"760_CR36","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/29.9.e45","volume":"29","author":"MW Pfaffl","year":"2001","unstructured":"Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9):e45","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"760_CR37","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1089\/ars.2007.1874","volume":"10","author":"BY Rubin","year":"2008","unstructured":"Rubin BY, Anderson SL, Kapas L (2008) Can the therapeutic efficacy of tocotrienols in neurodegenerative familial dysautonomia patients be measured clinically? Antioxidants Redox Signaling 10(4):837\u2013841","journal-title":"Antioxidants Redox Signaling"},{"issue":"3","key":"760_CR38","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1086\/318810","volume":"68","author":"SA Slaugenhaupt","year":"2001","unstructured":"Slaugenhaupt SA, Blumenfeld A, Gill SP, Leyne M, Mull J, Cuajungco MP, et al. (2001) Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia. Am J Human genet 68(3):598\u2013605","journal-title":"Am J Human genet"},{"issue":"4","key":"760_CR39","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1093\/hmg\/ddh046","volume":"13","author":"SA Slaugenhaupt","year":"2004","unstructured":"Slaugenhaupt SA, Mull J, Leyne M, Cuajungco MP, Gill SP, Hims MM, et al. (2004) Rescue of a human mRNA splicing defect by the plant cytokinin kinetin. Human Mol Genet 13(4):429\u2013436","journal-title":"Human Mol Genet"},{"key":"760_CR40","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0022-3476(63)80219-X","volume":"63","author":"AA Smith","year":"1963","unstructured":"Smith AA, Dancis J (1963) Response to intradermal histamine in familial dysautonomia\u2013a diagnostic test. J pediatrics 63:889\u2013894","journal-title":"J pediatrics"},{"issue":"3661","key":"760_CR41","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1126\/science.147.3661.1040","volume":"147","author":"A Smith","year":"1965","unstructured":"Smith A, Farbman A, Dancis J (1965) Absence of taste-Bud papillae in familial dysautonomia. Science 147(3661):1040\u20131041","journal-title":"Science"},{"issue":"40","key":"760_CR42","doi-asserted-by":"crossref","first-page":"10692","DOI":"10.1021\/bi00091a020","volume":"32","author":"YJ Suzuki","year":"1993","unstructured":"Suzuki YJ, Tsuchiya M, Wassall SR, Choo YM, Govil G, Kagan VE, et al. (1993) Structural and dynamic membrane properties of alpha-tocopherol and alpha-tocotrienol: implication to the molecular mechanism of their antioxidant potency. Biochemistry 32(40):10692\u201310699","journal-title":"Biochemistry"},{"issue":"4","key":"760_CR43","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1093\/ajcn\/40.4.747","volume":"40","author":"MG Traber","year":"1984","unstructured":"Traber MG, Kayden HJ (1984) Vitamin E is delivered to cells via the high affinity receptor for low-density lipoprotein. Am J Clin Nutr 40(4):747\u2013751","journal-title":"Am J Clin Nutr"}],"container-title":["Journal of Molecular Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12031-016-0760-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s12031-016-0760-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12031-016-0760-5","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,7]],"date-time":"2019-09-07T05:17:44Z","timestamp":1567833464000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s12031-016-0760-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,30]]},"references-count":43,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,7]]}},"alternative-id":["760"],"URL":"https:\/\/doi.org\/10.1007\/s12031-016-0760-5","relation":{},"ISSN":["0895-8696","1559-1166"],"issn-type":[{"value":"0895-8696","type":"print"},{"value":"1559-1166","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,30]]}}}