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Neurotherapeutics
Erschienen in: Neurotherapeutics 3/2015

01.07.2015 | Review

The Use of Induced Pluripotent Stem Cell Technology to Advance Autism Research and Treatment

verfasst von: Allan Acab, Alysson Renato Muotri

Erschienen in: Neurotherapeutics | Ausgabe 3/2015

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Abstract

Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders sharing a core set of symptoms, including impaired social interaction, language deficits, and repetitive behaviors. While ASDs are highly heritable and demonstrate a clear genetic component, the cellular and molecular mechanisms driving ASD etiology remain undefined. The unavailability of live patient-specific neurons has contributed to the difficulty in studying ASD pathophysiology. The recent advent of induced pluripotent stem cells (iPSCs) has provided the ability to generate patient-specific human neurons from somatic cells. The iPSC field has quickly grown, as researchers have demonstrated the utility of this technology to model several diseases, especially neurologic disorders. Here, we review the current literature around using iPSCs to model ASDs, and discuss the notable findings, and the promise and limitations of this technology. The recent report of a nonsyndromic ASD iPSC model and several previous ASD models demonstrating similar results points to the ability of iPSC to reveal potential novel biomarkers and therapeutics.
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Literatur
1.
Wing L, Gould J. Severe impairments of social interaction and associated abnormalities in children: epidemiology and classification. J Autism Dev Disord 1979;9:11-29.PubMed
2.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, American Psychiatric Association, Washington, DC.
3.
State MW, Levitt P. The conundrums of understanding genetic risks for autism spectrum disorders. Nat Neurosci 2011;14:1499-1506.PubMedCentralPubMed
4.
5.
Persico AM, Bourgeron T. Searching for ways out of the autism maze: genetic, epigenetic and environmental clues. Trends Neurosci 2006;29:349-358.PubMed
6.
O'Roak BJ, Vives L, Fu W, et al. Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science 2012;338:1619-1622.PubMedCentralPubMed
7.
Jiang YH, Yuen RK, Jin X, et al. Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing. Am J Hum Genet 2013;93:249-263.PubMedCentralPubMed
8.
Iossifov I, O'Roak BJ, Sanders SJ, et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature 2014;515:216-221.PubMedCentralPubMed
9.
De Rubeis S, He X, Goldberg AP, et al. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature 2014;515:209-215.PubMedCentralPubMed
10.
11.
Girirajan S, Rosenfeld JA, Coe BP, et al. Phenotypic heterogeneity of genomic disorders and rare copy-number variants. N Engl J Med 2012;367:1321-1331.PubMedCentralPubMed
12.
Steinberg J, Webber C. The roles of FMRP-regulated genes in autism spectrum disorder: single- and multiple-hit genetic etiologies. Am J Hum Genet 2013;93:825-839.PubMedCentralPubMed
13.
Leblond CS, Heinrich J, Delorme R, Proepper C, Betancur C, Huguet G. Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders. PLoS Genet 2012;8:e1002521.PubMedCentralPubMed
14.
15.
Kim S, Webster MJ. Postmortem brain tissue for drug discovery in psychiatric research. Schizophr Bull 2009;35:1031-1033.PubMedCentralPubMed
16.
17.
Lewis MH, Tanimura Y, Lee LW, Bodfish JW. Animal models of restricted repetitive behavior in autism. Behav Brain Res 2007;176:66-74.PubMedCentralPubMed
18.
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006;126:663-676.PubMed
19.
Soldner F, Jaenisch R. Medicine. iPSC disease modeling. Science 2012;338:1155-1156.PubMed
20.
21.
Chailangkarn T, Acab A, Muotri AR. Modeling neurodevelopmental disorders using human neurons. Curr Opin Neurobiol 2012;22:785-790.PubMedCentralPubMed
22.
Tiscornia G, Vivas EL, Izpisua Belmonte JC. Diseases in a dish: modeling human genetic disorders using induced pluripotent cells. Nat Med 2011;17:1570-1576.PubMed
23.
Raya A, Rodriguez-Piza I, Guenechea G, et al. Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature 2009;460:53-59.PubMedCentralPubMed
24.
Moretti A, Bellin M, Welling A, et al. Patient-specific induced pluripotent stem-cell models for long-QT syndrome. N Engl J Med 2010;363:1397-1409.PubMed
25.
Itzhaki I, Maizels L, Huber I, et al. Modelling the long QT syndrome with induced pluripotent stem cells. Nature 2011;471:225-229.PubMed
26.
Carvajal-Vergara X, Sevilla A, D'Souza SL, et al. Patient-specific induced pluripotent stem-cell-derived models of LEOPARD syndrome. Nature 2010;465:808-812.PubMedCentralPubMed
27.
Marchetto MC, Brennand KJ, Boyer LF, Gage FH. Induced pluripotent stem cells (iPSCs) and neurological disease modeling: progress and promises. Hum Mol Genet 2011;20:R109-R115.PubMedCentralPubMed
28.
Dimos JT, Rodolfa KT, Niakan KK, et al. Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 2008;321:1218-1221.PubMed
29.
Soldner F, Hockemeyer D, Beard C, et al. Parkinson's disease patient-derived induced pluripotent stem cells free of viral reprogramming factors. Cell 2009;136:964-977.PubMedCentralPubMed
30.
Israel MA, Yuan SH, Bardy C, et al. Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells. Nature 2012;482:216-220.PubMedCentralPubMed
31.
Mitne-Neto M, Machado-Costa M, Marchetto MC, et al. Downregulation of VAPB expression in motor neurons derived from induced pluripotent stem cells of ALS8 patients. Hum Mol Genet 2011;20:3642-3652.PubMedCentralPubMed
32.
Jiang H, Ren Y, Yuen EY, et al. Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells. Nat Commun 2012;3:668.PubMedCentralPubMed
33.
Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science 1992;256:184-185.PubMed
34.
McLean CA, Cherny RA, Fraser FW, et al. Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann Neurol 1999;46:860-866.PubMed
35.
Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 2002;297:353-356.PubMed
36.
Brennand KJ, Simone A, Jou J, et al. Modelling schizophrenia using human induced pluripotent stem cells. Nature 2011;473:221-225.PubMedCentralPubMed
37.
Andrade LN, Nathanson JL, Yeo GW, Menck CF, Muotri AR. Evidence for premature aging due to oxidative stress in iPSCs from Cockayne syndrome. Hum Mol Genet 2012;21:3825-3834.PubMedCentralPubMed
38.
Urbach A, Bar-Nur O, Daley GQ, Benvenisty N. Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell 2010;6:407-411.PubMedCentralPubMed
39.
Marchetto MC, Carromeu C, Acab A, Yu D, Yeo GW, Mu Y. A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 2010;143:527-539.PubMedCentralPubMed
40.
Goldstein S, Reynolds CR. Handbook of neurodevelopmental and genetic disorders in adults, Guilford Press, New York, 2005.
41.
Mitchell KJ. The genetics of neurodevelopmental disease. Curr Opin Neurobiol 2011;21:197-203.PubMed
42.
Zoghbi HY. Postnatal neurodevelopmental disorders: meeting at the synapse? Science 2003;302:826-830.PubMed
43.
Weinberger DR. Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 1987;44:660-669.PubMed
44.
Harrison PJ, Weinberger DR. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 2005;10:40-68.PubMed
45.
Schizophrenia Psychiatric Genome-Wide Association Study C. Genome-wide association study identifies five new schizophrenia loci. Nat Genet 2011;43:969-976.
46.
Ripke S, O'Dushlaine C, Chambert K, et al. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat Genet 2013;45:1150-1159.PubMed
47.
Xu B, Roos JL, Dexheimer P, et al. Exome sequencing supports a de novo mutational paradigm for schizophrenia. Nat Genet 2011;43:864-868.PubMedCentralPubMed
48.
Murray RM, Lewis SW. Is schizophrenia a neurodevelopmental disorder? Br Med J (Clin Res Ed) 1987;295:681-682.
49.
Thompson JL, Pogue-Geile MF, Grace AA. Developmental pathology, dopamine, and stress: a model for the age of onset of schizophrenia symptoms. Schizophr Bull 2004;30:875-900.PubMed
50.
Rapoport JL, Giedd JN, Gogtay N. Neurodevelopmental model of schizophrenia: update 2012. Mol Psychiatry 2012;17:1228-1238.PubMedCentralPubMed
51.
Selemon LD, Goldman-Rakic PS. The reduced neuropil hypothesis: a circuit based model of schizophrenia. Biol Psychiatry 1999;45:17-25.PubMed
52.
Jaaro-Peled H, Ayhan Y, Pletnikov MV, Sawa A. Review of pathological hallmarks of schizophrenia: comparison of genetic models with patients and nongenetic models. Schizophr Bull 2010;36:301-313.PubMedCentralPubMed
53.
Pasca SP, Portmann T, Voineagu I, et al. Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. Nat Med 2011;17:1657-1662.PubMedCentralPubMed
54.
Amenduni M, De Filippis R, Cheung AY, et al. iPS cells to model CDKL5-related disorders. Eur J Hum Genet 2011;19:1246-1255.PubMedCentralPubMed
55.
Verkerk AJ, Pieretti M, Sutcliffe JS, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991;65:905-914.PubMed
56.
Rogers SJ, Wehner DE, Hagerman R. The behavioral phenotype in fragile X: symptoms of autism in very young children with fragile X syndrome, idiopathic autism, and other developmental disorders. J Dev Behav Pediatr 2001;22:409-417.PubMed
57.
Kindler S, Kreienkamp HJ. The role of the postsynaptic density in the pathology of the fragile X syndrome. Results Probl Cell Differ 2012;54:61-80.PubMed
58.
Bassell GJ, Warren ST. Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function. Neuron 2008;60:201-214.PubMedCentralPubMed
59.
Eiges R, Urbach A, Malcov M, et al. Developmental study of fragile X syndrome using human embryonic stem cells derived from preimplantation genetically diagnosed embryos. Cell Stem Cell 2007;1:568-577.PubMed
60.
Sheridan SD, Theriault KM, Reis SA, et al. Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome. PLoS One 2011;6:e26203.PubMedCentralPubMed
61.
Liu J, Koscielska KA, Cao Z, et al. Signaling defects in iPSC-derived fragile X premutation neurons. Hum Mol Genet 2012;21:3795-3805.PubMedCentralPubMed
62.
Hagerman R, Hagerman P. Advances in clinical and molecular understanding of the FMR1 premutation and fragile X-associated tremor/ataxia syndrome. Lancet Neurol 2013;12:786-798.PubMedCentralPubMed
63.
Doers ME, Musser MT, Nichol R, et al. iPSC-derived forebrain neurons from FXS individuals show defects in initial neurite outgrowth. Stem Cells Dev 2014;23:1777-1787.PubMed
64.
Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell 2004;119:19-31.PubMed
65.
Bader PL, Faizi M, Kim LH, et al. Mouse model of Timothy syndrome recapitulates triad of autistic traits. Proc Natl Acad Sci U S A 2011;108:15432-15437.PubMedCentralPubMed
66.
Barttfeld P, Wicker B, Cukier S, Navarta S, Lew S, Sigman M. A big-world network in ASD: dynamical connectivity analysis reflects a deficit in long-range connections and an excess of short-range connections. Neuropsychologia 2011;49:254-263.PubMed
67.
Krey JF, Pasca SP, Shcheglovitov A, et al. Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons. Nat Neurosci 2013;16:201-209.PubMedCentralPubMed
68.
Knoll JH, Nicholls RD, Magenis RE, Graham JM, Jr., Lalande M, Latt SA. Angelman and Prader-Willi syndromes share a common chromosome 15 deletion but differ in parental origin of the deletion. Am J Med Genet 1989;32:285-290.PubMed
69.
Kishino T, Lalande M, Wagstaff J. UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet 1997;15:70-73.PubMed
70.
Bittel DC, Butler MG. Prader-Willi syndrome: clinical genetics, cytogenetics and molecular biology. Expert Rev Mol Med 2005;7:1-20.PubMed
71.
Thibert RL, Larson AM, Hsieh DT, Raby AR, Thiele EA. Neurologic manifestations of Angelman syndrome. Pediatr Neurol 2013;48:271-279.PubMed
72.
Whittington J, Holland A. Neurobehavioral phenotype in Prader-Willi syndrome. Am J Med Genet C Semin Med Genet 2010;154C:438-447.PubMed
73.
Chamberlain SJ, Chen PF, Ng KY, et al. Induced pluripotent stem cell models of the genomic imprinting disorders Angelman and Prader-Willi syndromes. Proc Natl Acad Sci U S A 2010;107:17668-17673.PubMedCentralPubMed
74.
Wilson HL, Wong AC, Shaw SR, et al. Molecular characterisation of the 22q13 deletion syndrome supports the role of haploinsufficiency of SHANK3/PROSAP2 in the major neurological symptoms. J Med Genet 2003;40:575-584.PubMedCentralPubMed
75.
76.
Naisbitt S, Kim E, Tu JC, et al. Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron 1999;23:569-582.PubMed
77.
Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet 2007;39:25-27.PubMedCentralPubMed
78.
Wang X, McCoy PA, Rodriguiz RM, et al. Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum Mol Genet 2011;20:3093-3108.PubMedCentralPubMed
79.
Shcheglovitov A, Shcheglovitova O, Yazawa M, et al. SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients. Nature 2013;503:267-271.PubMed
80.
Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 1999;23:185-188.PubMed
81.
Schanen C, Francke U. A severely affected male born into a Rett syndrome kindred supports X-linked inheritance and allows extension of the exclusion map. Am J Hum Genet 1998;63:267-269.PubMedCentralPubMed
82.
Villard L, Kpebe A, Cardoso C, Chelly PJ, Tardieu PM, Fontes M. Two affected boys in a Rett syndrome family: clinical and molecular findings. Neurology 2000;55:1188-1193.PubMed
83.
Chahrour M, Zoghbi HY. The story of Rett syndrome: from clinic to neurobiology. Neuron 2007;56:422-437.PubMed
84.
Williamson SL, Christodoulou J. Rett syndrome: new clinical and molecular insights. Eur J Hum Genet 2006;14:896-903.PubMed
85.
86.
Belichenko PV, Hagberg B, Dahlstrom A. Morphological study of neocortical areas in Rett syndrome. Acta Neuropathol 1997;93:50-61.PubMed
87.
Armstrong DD, Dunn K, Antalffy B. Decreased dendritic branching in frontal, motor and limbic cortex in Rett syndrome compared with trisomy 21. J Neuropathol Exp Neurol 1998;57:1013-1017.PubMed
88.
Ballas N, Lioy DT, Grunseich C, Mandel G. Non-cell autonomous influence of MeCP2-deficient glia on neuronal dendritic morphology. Nat Neurosci 2009;12:311-317.PubMedCentralPubMed
89.
Maezawa I, Swanberg S, Harvey D, LaSalle JM, Jin LW. Rett syndrome astrocytes are abnormal and spread MeCP2 deficiency through gap junctions. J Neurosci 2009;29:5051-5061.PubMedCentralPubMed
90.
Lioy DT, Garg SK, Monaghan CE, et al. A role for glia in the progression of Rett's syndrome. Nature 2011;475:497-500.PubMedCentralPubMed
91.
Okabe Y, Takahashi T, Mitsumasu C, Kosai K, Tanaka E, Matsuishi T. Alterations of gene expression and glutamate clearance in astrocytes derived from an MeCP2-null mouse model of Rett syndrome. PLoS One 2012;7:e35354.PubMedCentralPubMed
92.
Maezawa I, Jin LW. Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate. J Neurosci 2010;30:5346-5356.PubMed
93.
Derecki NC, Cronk JC, Lu Z, et al. Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 2012;484:105-109.PubMedCentralPubMed
94.
Nguyen MV, Felice CA, Du F, et al. Oligodendrocyte lineage cells contribute unique features to Rett syndrome neuropathology. J Neurosci 2013;33:18764-18774.PubMedCentralPubMed
95.
Guy J, Hendrich B, Holmes M, Martin JE, Bird A. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet 2001;27:322-326.PubMed
96.
Guy J, Gan J, Selfridge J, Cobb S, Bird A. Reversal of neurological defects in a mouse model of Rett syndrome. Science 2007;315:1143-1147.PubMed
97.
Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science 2008;320:1224-1229.PubMedCentralPubMed
98.
Skene PJ, Illingworth RS, Webb S, et al. Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state. Mol Cell 2010;37:457-468.PubMedCentralPubMed
99.
Dudek H, Datta SR, Franke TF, et al. Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 1997;275:661-665.PubMed
100.
O'Kusky JR, Ye P, D'Ercole AJ. Insulin-like growth factor-I promotes neurogenesis and synaptogenesis in the hippocampal dentate gyrus during postnatal development. J Neurosci 2000;20:8435-8442.PubMed
101.
Muotri AR, Marchetto MC, Coufal NG, Oefner R, Yeo G, Nakashima K. L1 retrotransposition in neurons is modulated by MeCP2. Nature 2010;468:443-446.PubMedCentralPubMed
102.
Cheung AY, Horvath LM, Grafodatskaya D, et al. Isolation of MECP2-null Rett Syndrome patient hiPS cells and isogenic controls through X-chromosome inactivation. Hum Mol Genet 2011;20:2103-2115.PubMedCentralPubMed
103.
Kim KY, Hysolli E, Park IH. Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome. Proc Natl Acad Sci U S A 2011;108:14169-14174.PubMedCentralPubMed
104.
Williams EC, Zhong X, Mohamed A, et al. Mutant astrocytes differentiated from Rett syndrome patients-specific iPSCs have adverse effects on wild-type neurons. Hum Mol Genet 2014;23:2968-2980.PubMedCentralPubMed
105.
Baudouin SJ. [Mouse models of autism: a common basis for syndromic and non syndromic autisms ?]. Med Sci (Paris) 2013;29:121-123 (in French).
106.
Marshall CR, Noor A, Vincent JB, Lionel AC, Feuk L, Skaug J. Structural variation of chromosomes in autism spectrum disorder. Am J Hum Genet 2008;82:477-488.PubMedCentralPubMed
107.
Yonan AL, Alarcon M, Cheng R, et al. A genomewide screen of 345 families for autism-susceptibility loci. Am J Hum Genet 2003;73:886-897.PubMedCentralPubMed
108.
O'Roak BJ, Vives L, Girirajan S, Karakoc E, Krumm N, Coe BP. Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 2012;485:246-250.PubMedCentralPubMed
109.
Lawson-Yuen A, Saldivar JS, Sommer S, Picker J. Familial deletion within NLGN4 associated with autism and Tourette syndrome. Eur J Hum Genet 2008;16:614-618.PubMed
110.
Rubenstein JL, Merzenich MM. Model of autism: increased ratio of excitation/inhibition in key neural systems. Genes Brain Behav 2003;2:255-267.PubMed
111.
Jamain S, Betancur C, Quach H, et al. Linkage and association of the glutamate receptor 6 gene with autism. Mol Psychiatry 2002;7:302-310.PubMedCentralPubMed
112.
113.
Rasin MR, Gazula VR, Breunig JJ, et al. Numb and Numbl are required for maintenance of cadherin-based adhesion and polarity of neural progenitors. Nat Neurosci 2007;10:819-827.PubMed
114.
Hemara-Wahanui A, Berjukow S, Hope CI, Dearden PK, Wu SB, Wilson-Wheeler J. A CACNA1F mutation identified in an X-linked retinal disorder shifts the voltage dependence of Cav1.4 channel activation. Proc Natl Acad Sci USA 2005;102:7553-7558.PubMedCentralPubMed
115.
Krey JF, Dolmetsch RE. Molecular mechanisms of autism: a possible role for Ca2+ signaling. Curr Opin Neurobiol 2007;17:112-119.PubMed
116.
Griesi-Oliveira K, Acab A, Gupta AR, et al. Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons. Mol Psychiatry 2014 Nov 11.
117.
Li Y, Jia YC, Cui K, Li N, Zheng ZY, Wang YZ. Essential role of TRPC channels in the guidance of nerve growth cones by brain-derived neurotrophic factor. Nature 2005;434:894-898.PubMed
118.
Zhou J, Du W, Zhou K, Tai Y, Yao H, Jia Y. Critical role of TRPC6 channels in the formation of excitatory synapses. Nat Neurosci 2008;11:741-743.PubMed
119.
Leuner K, Li W, Amaral MD, Rudolph S, Calfa G, Schuwald AM. Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca(2+)-permeable TRPC6 channels. Hippocampus 2012;23:40-52.PubMedCentralPubMed
120.
Tai Y, Feng S, Ge R, Du W, Zhang X, He Z. TRPC6 channels promote dendritic growth via the CaMKIV-CREB pathway. J Cell Sci 2008;121:2301-2307.PubMed
121.
Heiser JH, Schuwald AM, Sillani G, Ye L, Muller WE, Leuner K. TRPC6 channel-mediated neurite outgrowth in PC12 cells and hippocampal neurons involves activation of RAS/MEK/ERK, PI3K, and CAMKIV signaling. J Neurochem 2013;127:303-313.PubMed
122.
Li W, Calfa G, Larimore J, Pozzo-Miller L. Activity-dependent BDNF release and TRPC signaling is impaired in hippocampal neurons of Mecp2 mutant mice. Proc Natl Acad Sci USA 2012;109:17087-17092.PubMedCentralPubMed
123.
Im HI, Hollander JA, Bali P, Kenny PJ. MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212. Nat Neurosci 2010;13:1120-1127.PubMedCentralPubMed
124.
Kline DD, Ogier M, Kunze DL, Katz DM. Exogenous brain-derived neurotrophic factor rescues synaptic dysfunction in Mecp2-null mice. J Neurosci 2010;30:5303-5310.PubMedCentralPubMed
125.
Zhou Z, Hong EJ, Cohen S, et al. Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation. Neuron 2006;52:255-269.PubMedCentralPubMed
126.
Yuan SH, Martin J, Elia J, et al. Cell-surface marker signatures for the isolation of neural stem cells, glia and neurons derived from human pluripotent stem cells. PLoS One 2011;6:e17540.PubMedCentralPubMed
127.
Miller JC, Tan S, Qiao G, et al. A TALE nuclease architecture for efficient genome editing. Nat Biotechnol 2011;29:143-148.PubMed
128.
129.
Beltrao-Braga PI, Pignatari GC, Maiorka PC, Oliveira NA, Lizier NF, Wenceslau CV. Feeder-free derivation of induced pluripotent stem cells from human immature dental pulp stem cells. Cell Transplant 2011;20:1707-1719.PubMed
130.
Li LB, Chang KH, Wang PR, Hirata RK, Papayannopoulou T, Russell DW. Trisomy correction in Down syndrome induced pluripotent stem cells. Cell Stem Cell 2012;11:615-619.PubMedCentralPubMed
131.
Shi Y, Kirwan P, Smith J, MacLean G, Orkin SH, Livesey FJ. A human stem cell model of early Alzheimer's disease pathology in Down syndrome. Sci Transl Med 2012;4:124ra29.PubMedCentralPubMed
132.
Lu HE, Yang YC, Chen SM, et al. Modeling neurogenesis impairment in Down syndrome with induced pluripotent stem cells from Trisomy 21 amniotic fluid cells. Exp Cell Res 2013;319:498-505.PubMed
133.
Weick JP, Held DL, Bonadurer GF, 3rd, et al. Deficits in human trisomy 21 iPSCs and neurons. Proc Natl Acad Sci U S A 2013;110:9962-9967.PubMedCentralPubMed
134.
Hibaoui Y, Grad I, Letourneau A, et al. Modelling and rescuing neurodevelopmental defect of Down syndrome using induced pluripotent stem cells from monozygotic twins discordant for trisomy 21. EMBO Mol Med 2014;6:259-277.PubMedCentralPubMed
135.
Chen C, Jiang P, Xue H, et al. Role of astroglia in Down's syndrome revealed by patient-derived human-induced pluripotent stem cells. Nat Commun 2014;5:4430.PubMedCentralPubMed
136.
Yang J, Cai J, Zhang Y, et al. Induced pluripotent stem cells can be used to model the genomic imprinting disorder Prader-Willi syndrome. J Biol Chem 2010;285:40303-11.
Metadaten
Titel
The Use of Induced Pluripotent Stem Cell Technology to Advance Autism Research and Treatment
verfasst von
Allan Acab
Alysson Renato Muotri
Publikationsdatum
01.07.2015
Verlag
Springer US
Erschienen in
Neurotherapeutics / Ausgabe 3/2015
Print ISSN: 1933-7213
Elektronische ISSN: 1878-7479
DOI
https://doi.org/10.1007/s13311-015-0354-x

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Akuter Schwindel: Wann lohnt sich eine MRT?

28.04.2024 Schwindel Nachrichten

Akuter Schwindel stellt oft eine diagnostische Herausforderung dar. Wie nützlich dabei eine MRT ist, hat eine Studie aus Finnland untersucht. Immerhin einer von sechs Patienten wurde mit akutem ischämischem Schlaganfall diagnostiziert.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Update Neurologie

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