Home > Publications Database > Human iPSC models of neuronal ceroid lipofuscinosis capture distinct effects of TPP1 and CLN3 mutations on the endocytic pathway. > print

001     137321
005     20240321220229.0
024 7 _ |a 10.1093/hmg/ddt596
|2 doi
024 7 _ |a pmid:24271013
|2 pmid
024 7 _ |a pmc:PMC3959814
|2 pmc
024 7 _ |a 0964-6906
|2 ISSN
024 7 _ |a 1460-2083
|2 ISSN
024 7 _ |a altmetric:1930383
|2 altmetric
037 _ _ |a DZNE-2020-03643
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Lojewski, Xenia
|b 0
245 _ _ |a Human iPSC models of neuronal ceroid lipofuscinosis capture distinct effects of TPP1 and CLN3 mutations on the endocytic pathway.
260 _ _ |a Oxford
|c 2014
|b Oxford Univ. Press
264 _ 1 |3 online
|2 Crossref
|b Oxford University Press (OUP)
|c 2013-11-23
264 _ 1 |3 print
|2 Crossref
|b Oxford University Press (OUP)
|c 2014-04-15
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1592316169_23892
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a Neuronal ceroid lipofuscinosis (NCL) comprises ∼13 genetically distinct lysosomal disorders primarily affecting the central nervous system. Here we report successful reprograming of patient fibroblasts into induced pluripotent stem cells (iPSCs) for the two most common NCL subtypes: classic late-infantile NCL, caused by TPP1(CLN2) mutation, and juvenile NCL, caused by CLN3 mutation. CLN2/TPP1- and CLN3-iPSCs displayed overlapping but distinct biochemical and morphological abnormalities within the endosomal-lysosomal system. In neuronal derivatives, further abnormalities were observed in mitochondria, Golgi and endoplasmic reticulum. While lysosomal storage was undetectable in iPSCs, progressive disease subtype-specific storage material was evident upon neural differentiation and was rescued by reintroducing the non-mutated NCL proteins. In proof-of-concept studies, we further documented differential effects of potential small molecule TPP1 activity inducers. Fenofibrate and gemfibrozil, previously reported to induce TPP1 activity in control cells, failed to increase TPP1 activity in patient iPSC-derived neural progenitor cells. Conversely, nonsense suppression by PTC124 resulted in both an increase of TPP1 activity and attenuation of neuropathology in patient iPSC-derived neural progenitor cells. This study therefore documents the high value of this powerful new set of tools for improved drug screening and for investigating early mechanisms driving NCL pathogenesis.
536 _ _ |a 344 - Clinical and Health Care Research (POF3-344)
|0 G:(DE-HGF)POF3-344
|c POF3-344
|f POF III
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a CLN3 protein, human
|2 NLM Chemicals
650 _ 7 |a Membrane Glycoproteins
|2 NLM Chemicals
650 _ 7 |a Molecular Chaperones
|2 NLM Chemicals
650 _ 7 |a Serine Proteases
|0 EC 3.4.-
|2 NLM Chemicals
650 _ 7 |a Aminopeptidases
|0 EC 3.4.11.-
|2 NLM Chemicals
650 _ 7 |a Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
|0 EC 3.4.14.-
|2 NLM Chemicals
650 _ 7 |a tripeptidyl-peptidase 1
|0 EC 3.4.14.9
|2 NLM Chemicals
650 _ 7 |a Gemfibrozil
|0 Q8X02027X3
|2 NLM Chemicals
650 _ 7 |a Fenofibrate
|0 U202363UOS
|2 NLM Chemicals
650 _ 2 |a Aminopeptidases: genetics
|2 MeSH
650 _ 2 |a Aminopeptidases: metabolism
|2 MeSH
650 _ 2 |a Blotting, Western
|2 MeSH
650 _ 2 |a Case-Control Studies
|2 MeSH
650 _ 2 |a Cell Proliferation
|2 MeSH
650 _ 2 |a Cells, Cultured
|2 MeSH
650 _ 2 |a Dipeptidyl-Peptidases and Tripeptidyl-Peptidases: genetics
|2 MeSH
650 _ 2 |a Dipeptidyl-Peptidases and Tripeptidyl-Peptidases: metabolism
|2 MeSH
650 _ 2 |a Electrophysiology
|2 MeSH
650 _ 2 |a Endoplasmic Reticulum: drug effects
|2 MeSH
650 _ 2 |a Endoplasmic Reticulum: metabolism
|2 MeSH
650 _ 2 |a Fenofibrate: pharmacology
|2 MeSH
650 _ 2 |a Fibroblasts: drug effects
|2 MeSH
650 _ 2 |a Fibroblasts: metabolism
|2 MeSH
650 _ 2 |a Fibroblasts: pathology
|2 MeSH
650 _ 2 |a Gemfibrozil: pharmacology
|2 MeSH
650 _ 2 |a Golgi Apparatus: drug effects
|2 MeSH
650 _ 2 |a Golgi Apparatus: metabolism
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Immunoenzyme Techniques
|2 MeSH
650 _ 2 |a Induced Pluripotent Stem Cells: drug effects
|2 MeSH
650 _ 2 |a Induced Pluripotent Stem Cells: metabolism
|2 MeSH
650 _ 2 |a Induced Pluripotent Stem Cells: pathology
|2 MeSH
650 _ 2 |a Lysosomes: drug effects
|2 MeSH
650 _ 2 |a Lysosomes: metabolism
|2 MeSH
650 _ 2 |a Membrane Glycoproteins: genetics
|2 MeSH
650 _ 2 |a Membrane Glycoproteins: metabolism
|2 MeSH
650 _ 2 |a Models, Neurological
|2 MeSH
650 _ 2 |a Molecular Chaperones: genetics
|2 MeSH
650 _ 2 |a Molecular Chaperones: metabolism
|2 MeSH
650 _ 2 |a Mutation: genetics
|2 MeSH
650 _ 2 |a Neuronal Ceroid-Lipofuscinoses: genetics
|2 MeSH
650 _ 2 |a Neuronal Ceroid-Lipofuscinoses: metabolism
|2 MeSH
650 _ 2 |a Neuronal Ceroid-Lipofuscinoses: pathology
|2 MeSH
650 _ 2 |a Neurons: drug effects
|2 MeSH
650 _ 2 |a Neurons: metabolism
|2 MeSH
650 _ 2 |a Neurons: pathology
|2 MeSH
650 _ 2 |a Serine Proteases: genetics
|2 MeSH
650 _ 2 |a Serine Proteases: metabolism
|2 MeSH
700 1 _ |a Staropoli, John F
|b 1
700 1 _ |a Biswas-Legrand, Sunita
|b 2
700 1 _ |a Simas, Alexandra M
|b 3
700 1 _ |a Haliw, Larissa
|b 4
700 1 _ |a Selig, Martin K
|b 5
700 1 _ |a Coppel, Scott H
|b 6
700 1 _ |a Goss, Kendrick A
|b 7
700 1 _ |a Petcherski, Anton
|b 8
700 1 _ |a Chandrachud, Uma
|b 9
700 1 _ |a Sheridan, Steven D
|b 10
700 1 _ |a Lucente, Diane
|b 11
700 1 _ |a Sims, Katherine B
|b 12
700 1 _ |a Gusella, James F
|b 13
700 1 _ |a Sondhi, Dolan
|b 14
700 1 _ |a Crystal, Ronald G
|b 15
700 1 _ |a Reinhardt, Peter
|b 16
700 1 _ |a Sterneckert, Jared
|b 17
700 1 _ |a Schöler, Hans
|b 18
700 1 _ |a Haggarty, Stephen J
|b 19
700 1 _ |a Storch, Alexander
|0 P:(DE-2719)9000306
|b 20
|u dzne
700 1 _ |a Hermann, Andreas
|0 P:(DE-2719)2811732
|b 21
|u dzne
700 1 _ |a Cotman, Susan L
|0 P:(DE-HGF)0
|b 22
|e Corresponding author
773 1 8 |a 10.1093/hmg/ddt596
|b : Oxford University Press (OUP), 2013-11-23
|n 8
|p 2005-2022
|3 journal-article
|2 Crossref
|t Human Molecular Genetics
|v 23
|y 2013
|x 1460-2083
773 _ _ |a 10.1093/hmg/ddt596
|g Vol. 23, no. 8, p. 2005 - 2022
|0 PERI:(DE-600)1474816-2
|n 8
|q 23:8<2005 - 2022
|p 2005-2022
|t Human molecular genetics
|v 23
|y 2013
|x 1460-2083
856 7 _ |2 Pubmed Central
|u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959814
909 C O |o oai:pub.dzne.de:137321
|p VDB
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 20
|6 P:(DE-2719)9000306
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 21
|6 P:(DE-2719)2811732
913 1 _ |a DE-HGF
|b Forschungsbereich Gesundheit
|l Erkrankungen des Nervensystems
|1 G:(DE-HGF)POF3-340
|0 G:(DE-HGF)POF3-344
|2 G:(DE-HGF)POF3-300
|v Clinical and Health Care Research
|x 0
914 1 _ |y 2014
915 _ _ |a Nationallizenz
|0 StatID:(DE-HGF)0420
|2 StatID
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0310
|2 StatID
|b NCBI Molecular Biology Database
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0320
|2 StatID
|b PubMed Central
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b HUM MOL GENET : 2017
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
915 _ _ |a WoS
|0 StatID:(DE-HGF)0110
|2 StatID
|b Science Citation Index
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
915 _ _ |a WoS
|0 StatID:(DE-HGF)0111
|2 StatID
|b Science Citation Index Expanded
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1030
|2 StatID
|b Current Contents - Life Sciences
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
915 _ _ |a IF < 5
|0 StatID:(DE-HGF)9900
|2 StatID
920 1 _ |0 I:(DE-2719)5000014
|k AG Storch ; AG Storch 2 Rostock
|l Non-motor symptoms in Parkinson's disease
|x 0
920 1 _ |0 I:(DE-2719)1510100
|k Clinical Dementia Research Rostock /Greifswald ; AG Teipel
|l Clinical Dementia Research Rostock /Greifswald
|x 1
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a I:(DE-2719)5000014
980 _ _ |a I:(DE-2719)1510100
980 _ _ |a UNRESTRICTED
999 C 5 |a 10.1016/j.bbamcr.2008.11.004
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.bbamcr.2008.11.004
999 C 5 |y 2011
|2 Crossref
|t The Neuronal Ceroid Lipofuscinoses (Batten Disease)
|o Mole The Neuronal Ceroid Lipofuscinoses (Batten Disease) 2011
999 C 5 |y 1989
|2 Crossref
|o Palmer 1989
999 C 5 |y 2002
|2 Crossref
|o Kominami 2002
999 C 5 |a 10.2217/clp.11.70
|9 -- missing cx lookup --
|2 Crossref
|o 10.2217/clp.11.70
999 C 5 |a 10.1093/hmg/ddl466
|9 -- missing cx lookup --
|2 Crossref
|o 10.1093/hmg/ddl466
999 C 5 |a 10.1016/j.yexcr.2008.06.016
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.yexcr.2008.06.016
999 C 5 |a 10.1186/1471-2121-10-83
|9 -- missing cx lookup --
|2 Crossref
|o 10.1186/1471-2121-10-83
999 C 5 |a 10.1016/j.yexcr.2010.09.007
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.yexcr.2010.09.007
999 C 5 |a 10.1007/s00018-011-0913-1
|9 -- missing cx lookup --
|2 Crossref
|o 10.1007/s00018-011-0913-1
999 C 5 |a 10.1021/pr301125k
|9 -- missing cx lookup --
|2 Crossref
|o 10.1021/pr301125k
999 C 5 |a 10.1016/j.bbadis.2006.08.002
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.bbadis.2006.08.002
999 C 5 |a 10.1016/j.bbadis.2006.08.010
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.bbadis.2006.08.010
999 C 5 |a 10.1074/jbc.M602180200
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.M602180200
999 C 5 |a 10.1186/1471-2202-5-57
|9 -- missing cx lookup --
|2 Crossref
|o 10.1186/1471-2202-5-57
999 C 5 |a 10.1073/pnas.96.20.11341
|9 -- missing cx lookup --
|2 Crossref
|o 10.1073/pnas.96.20.11341
999 C 5 |a 10.1038/8861
|9 -- missing cx lookup --
|2 Crossref
|o 10.1038/8861
999 C 5 |a 10.1073/pnas.2136651100
|9 -- missing cx lookup --
|2 Crossref
|o 10.1073/pnas.2136651100
999 C 5 |a 10.1242/jcs.030122
|9 -- missing cx lookup --
|2 Crossref
|o 10.1242/jcs.030122
999 C 5 |a 10.1083/jcb.201102115
|9 -- missing cx lookup --
|2 Crossref
|o 10.1083/jcb.201102115
999 C 5 |a 10.1242/jcs.038323
|9 -- missing cx lookup --
|2 Crossref
|o 10.1242/jcs.038323
999 C 5 |a 10.1128/MCB.06726-11
|9 -- missing cx lookup --
|2 Crossref
|o 10.1128/MCB.06726-11
999 C 5 |a 10.1098/rstb.2011.0017
|9 -- missing cx lookup --
|2 Crossref
|o 10.1098/rstb.2011.0017
999 C 5 |a 10.1038/nsmb.2172
|9 -- missing cx lookup --
|2 Crossref
|o 10.1038/nsmb.2172
999 C 5 |a 10.1038/nature06534
|9 -- missing cx lookup --
|2 Crossref
|o 10.1038/nature06534
999 C 5 |a 10.1016/j.cell.2006.07.024
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.cell.2006.07.024
999 C 5 |a 10.1371/journal.pone.0026203
|9 -- missing cx lookup --
|2 Crossref
|o 10.1371/journal.pone.0026203
999 C 5 |a 10.1093/hmg/11.22.2709
|9 -- missing cx lookup --
|2 Crossref
|o 10.1093/hmg/11.22.2709
999 C 5 |a 10.1371/journal.pone.0017118
|9 -- missing cx lookup --
|2 Crossref
|o 10.1371/journal.pone.0017118
999 C 5 |a 10.1161/01.RES.0000065580.02404.F4
|9 -- missing cx lookup --
|2 Crossref
|o 10.1161/01.RES.0000065580.02404.F4
999 C 5 |a 10.1111/j.1440-1789.2007.00876.x
|9 -- missing cx lookup --
|2 Crossref
|o 10.1111/j.1440-1789.2007.00876.x
999 C 5 |a 10.1038/sj.mt.6300049
|9 -- missing cx lookup --
|2 Crossref
|o 10.1038/sj.mt.6300049
999 C 5 |a 10.1038/nature05756
|9 -- missing cx lookup --
|2 Crossref
|o 10.1038/nature05756
999 C 5 |a 10.1074/jbc.M112.365148
|9 -- missing cx lookup --
|2 Crossref
|o 10.1074/jbc.M112.365148
999 C 5 |a 10.1093/hmg/ddt120
|9 -- missing cx lookup --
|2 Crossref
|o 10.1093/hmg/ddt120
999 C 5 |a 10.1016/j.bbadis.2013.01.009
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.bbadis.2013.01.009
999 C 5 |a 10.1016/j.ajhg.2012.04.021
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/j.ajhg.2012.04.021
999 C 5 |a 10.1093/hmg/dds558
|9 -- missing cx lookup --
|2 Crossref
|o 10.1093/hmg/dds558
999 C 5 |a 10.1093/hmg/dds089
|9 -- missing cx lookup --
|2 Crossref
|o 10.1093/hmg/dds089
999 C 5 |a 10.1007/s11910-013-0366-z
|9 -- missing cx lookup --
|2 Crossref
|o 10.1007/s11910-013-0366-z
999 C 5 |a 10.1371/journal.pone.0055526
|9 -- missing cx lookup --
|2 Crossref
|o 10.1371/journal.pone.0055526
999 C 5 |a 10.1136/jcp.2005.027045
|9 -- missing cx lookup --
|2 Crossref
|o 10.1136/jcp.2005.027045
999 C 5 |a 10.1371/journal.pone.0038310
|9 -- missing cx lookup --
|2 Crossref
|o 10.1371/journal.pone.0038310
999 C 5 |a 10.1091/mbc.E05-11-1054
|9 -- missing cx lookup --
|2 Crossref
|o 10.1091/mbc.E05-11-1054
999 C 5 |a 10.1083/jcb.200302131
|9 -- missing cx lookup --
|2 Crossref
|o 10.1083/jcb.200302131
999 C 5 |a 10.2353/ajpath.2008.080684
|9 -- missing cx lookup --
|2 Crossref
|o 10.2353/ajpath.2008.080684
999 C 5 |a 10.1093/hmg/ddr285
|9 -- missing cx lookup --
|2 Crossref
|o 10.1093/hmg/ddr285
999 C 5 |a 10.1186/1756-6606-5-35
|9 -- missing cx lookup --
|2 Crossref
|o 10.1186/1756-6606-5-35
999 C 5 |a 10.1006/nbdi.1999.0267
|9 -- missing cx lookup --
|2 Crossref
|o 10.1006/nbdi.1999.0267
999 C 5 |a 10.1016/S0304-3940(99)00095-6
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/S0304-3940(99)00095-6
999 C 5 |a 10.1042/bj3340547
|9 -- missing cx lookup --
|2 Crossref
|o 10.1042/bj3340547
999 C 5 |a 10.1002/ajmg.10660
|9 -- missing cx lookup --
|2 Crossref
|o 10.1002/ajmg.10660
999 C 5 |a 10.1016/S0076-6879(06)20004-1
|9 -- missing cx lookup --
|2 Crossref
|o 10.1016/S0076-6879(06)20004-1
999 C 5 |a 10.1038/nature08436
|9 -- missing cx lookup --
|2 Crossref
|o 10.1038/nature08436
999 C 5 |a 10.1242/jcs.01307
|9 -- missing cx lookup --
|2 Crossref
|o 10.1242/jcs.01307
999 C 5 |a 10.1634/stemcells.2005-0192
|9 -- missing cx lookup --
|2 Crossref
|o 10.1634/stemcells.2005-0192
999 C 5 |a 10.1038/ncb2204
|9 -- missing cx lookup --
|2 Crossref
|o 10.1038/ncb2204
999 C 5 |a 10.4161/auto.19496
|9 -- missing cx lookup --
|2 Crossref
|o 10.4161/auto.19496
999 C 5 |a 10.1373/49.3.509
|9 -- missing cx lookup --
|2 Crossref
|o 10.1373/49.3.509
999 C 5 |a 10.1006/bbrc.2000.2207
|9 -- missing cx lookup --
|2 Crossref
|o 10.1006/bbrc.2000.2207
999 C 5 |a 10.1006/abbi.1993.1523
|9 -- missing cx lookup --
|2 Crossref
|o 10.1006/abbi.1993.1523
999 C 5 |a 10.1038/mt.2011.255
|9 -- missing cx lookup --
|2 Crossref
|o 10.1038/mt.2011.255
999 C 5 |a 10.1038/mt.2010.55
|9 -- missing cx lookup --
|2 Crossref
|o 10.1038/mt.2010.55
999 C 5 |a 10.1186/gb-2006-7-10-r100
|9 -- missing cx lookup --
|2 Crossref
|o 10.1186/gb-2006-7-10-r100

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21