دورية أكاديمية
أعرض في EDS

Abnormal polyamine metabolism is unique to the neuropathic forms of MPS: potential for biomarker development and insight into pathogenesis.

التفاصيل البيبلوغرافية
العنوان: Abnormal polyamine metabolism is unique to the neuropathic forms of MPS: potential for biomarker development and insight into pathogenesis.
المؤلفون: Hinderer C; Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Katz N; Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Louboutin JP; Section of Anatomy, Department of Basic Medical Sciences, University of the West Indies, Kingston, Jamaica., Bell P; Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Tolar J; Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA., Orchard PJ; Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA., Lund TC; Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN 55455, USA., Nayal M; Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Weng L; Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA., Mesaros C; Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA., de Souza CFM; Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, RS Porto Alegre 90035-903, Brazil., Dalla Corte A; Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, RS Porto Alegre 90035-903, Brazil.; Post-Graduate Course in Medical Sciences, UFRGS, Porto Alegre, RS 90035-003, Brazil., Giugliani R; Medical Genetics Service, HCPA.; Post-Graduate Course in Medical Sciences, UFRGS, Porto Alegre, RS 90035-003, Brazil., Wilson JM; Gene Therapy Program, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
المصدر: Human molecular genetics [Hum Mol Genet] 2017 Oct 01; Vol. 26 (19), pp. 3837-3849.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: IRL Press at Oxford University Press Country of Publication: England NLM ID: 9208958 Publication Model: Print Cited Medium: Internet ISSN: 1460-2083 (Electronic) Linking ISSN: 09646906 NLM ISO Abbreviation: Hum Mol Genet Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford, England ; New York : IRL Press at Oxford University Press, c1992-
مواضيع طبية MeSH: Mucopolysaccharidoses/*metabolism , Polyamines/*metabolism, Adolescent ; Animals ; Biomarkers/cerebrospinal fluid ; Central Nervous System Diseases/diagnosis ; Child ; Disease Models, Animal ; Dogs ; Enzyme Replacement Therapy/methods ; Female ; Genetic Therapy/methods ; Humans ; Male ; Mice ; Mucopolysaccharidoses/cerebrospinal fluid ; Mucopolysaccharidosis I/cerebrospinal fluid ; Mucopolysaccharidosis I/diagnosis ; Mucopolysaccharidosis I/metabolism ; Spermine/analysis ; Spermine/cerebrospinal fluid ; Spermine/chemistry
مستخلص: The mucopolysaccharidoses (MPS) are rare genetic disorders marked by severe somatic and neurological symptoms. Development of treatments for the neurological manifestations of MPS has been hindered by the lack of objective measures of central nervous system disease burden. Identification of biomarkers for central nervous system disease in MPS patients would facilitate the evaluation of new agents in clinical trials. High throughput metabolite screening of cerebrospinal fluid (CSF) samples from a canine model of MPS I revealed a marked elevation of the polyamine, spermine, in affected animals, and gene therapy studies demonstrated that reduction of CSF spermine reflects correction of brain lesions in these animals. In humans, CSF spermine was elevated in neuropathic subtypes of MPS (MPS I, II, IIIA, IIIB), but not in subtypes in which cognitive function is preserved (MPS IVA, VI). In MPS I patients, elevated CSF spermine was restricted to patients with genotypes associated with CNS disease and was reduced following hematopoietic stem cell transplantation, which is the only therapy currently capable of improving cognitive outcomes. Additional studies in cultured neurons from MPS I mice showed that elevated spermine was essential for the abnormal neurite overgrowth exhibited by MPS neurons. These findings offer new insights into the pathogenesis of CNS disease in MPS patients, and support the use of spermine as a new biomarker to facilitate the development of next generation therapeutics for MPS.
(© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
References: Nucleic Acids Res. 2015 Jul 1;43(W1):W251-7. (PMID: 25897128)
Pediatrics. 2009 Jan;123(1):229-40. (PMID: 19117887)
Genomics. 1992 Nov;14(3):763-8. (PMID: 1339393)
Mol Ther. 2015 Aug;23 (8):1298-1307. (PMID: 26022732)
Neuron. 2004 Nov 18;44(4):609-21. (PMID: 15541310)
Am J Pathol. 1984 Mar;114(3):487-95. (PMID: 6320652)
Orphanet J Rare Dis. 2008 Sep 16;3:24. (PMID: 18796143)
Neuron. 2002 Aug 15;35(4):711-9. (PMID: 12194870)
J Neurosci Res. 2010 Jan;88(1):202-13. (PMID: 19658197)
Bone Marrow Transplant. 2003 Jun;31(12):1105-17. (PMID: 12796790)
Bone Marrow Transplant. 2007 Aug;40(3):225-33. (PMID: 17529997)
Hum Mol Genet. 2011 Sep 15;20(18):3653-66. (PMID: 21685203)
Biochem J. 1999 Mar 1;338 ( Pt 2):317-23. (PMID: 10024506)
Mol Ther. 2014 Dec;22(12):2018-27. (PMID: 25027660)
Glycobiology. 2000 Jun;10(6):577-86. (PMID: 10814699)
Biol Blood Marrow Transplant. 2008 May;14(5):485-98. (PMID: 18410891)
Mol Cell Neurosci. 2009 May;41(1):8-18. (PMID: 19386237)
Nucleic Acids Res. 2012 Jul;40(Web Server issue):W127-33. (PMID: 22553367)
Am J Med Genet. 1993 Apr 15;46(2):209-18. (PMID: 8484412)
Glycobiology. 2006 Dec;16(12 ):1251-61. (PMID: 16971378)
Blood. 2005 Sep 15;106(6):1956-64. (PMID: 15947088)
J Neurosci. 2009 Jul 29;29(30):9545-52. (PMID: 19641117)
J Pediatr. 2004 May;144(5):581-8. (PMID: 15126990)
Pediatrics. 2007 Jul;120(1):e37-46. (PMID: 17606547)
Cytometry A. 2004 Apr;58(2):167-76. (PMID: 15057970)
Mol Genet Metab. 2013 Sep-Oct;110(1-2):54-64. (PMID: 23665161)
Mol Genet Metab. 2016 Sep;119(1-2):124-30. (PMID: 27386755)
N Engl J Med. 2004 May 6;350(19):1960-9. (PMID: 15128896)
Am J Cardiol. 2003 Oct 1;92 (7):882-6. (PMID: 14516901)
J Biol Chem. 2001 Dec 14;276(50):46779-91. (PMID: 11577085)
Neuroscience. 2004;128(4):741-9. (PMID: 15464282)
J Biol Chem. 2003 Nov 21;278(47):47181-9. (PMID: 12972423)
J Neurosci Res. 2002 Jul 1;69(1):30-8. (PMID: 12111813)
NMR Biomed. 2014 Jan;27(1):53-66. (PMID: 23904127)
Nucleic Acids Res. 2009 Jul;37(Web Server issue):W652-60. (PMID: 19429898)
Appl Clin Genet. 2015 Oct 30;8:245-55. (PMID: 26586959)
Mol Genet Metab. 2003 Jan;78(1):37-43. (PMID: 12559846)
Int J Oncol. 2008 Apr;32(4):749-56. (PMID: 18360702)
Metab Brain Dis. 2011 Mar;26(1):9-19. (PMID: 21225451)
معلومات مُعتمدة: P30 ES013508 United States ES NIEHS NIH HHS; T32 ES019851 United States ES NIEHS NIH HHS
المشرفين على المادة: 0 (Biomarkers)
0 (Polyamines)
2FZ7Y3VOQX (Spermine)
تواريخ الأحداث: Date Created: 20170922 Date Completed: 20180123 Latest Revision: 20181113
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5886077
DOI: 10.1093/hmg/ddx277
PMID: 28934395
قاعدة البيانات: MEDLINE
الوصف
تدمد:1460-2083
DOI:10.1093/hmg/ddx277