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... Prize in 2012 in recognition to his discovery. After this pioneer work many efforts have been done to successfully reproduce this result in human fibroblasts [114] as well as optimize the protocol by changing the transcriptional factors [115], as well as substituting them by small molecules [116–118] or miRNAs [119–121] for transcription factors. An increasing number of papers have come out in the last few years using fibroblasts for the generation of induced pluripotent stem cells (iPS), some of which are focused in the generation of neurons from these iPS for the study of Alzheimer disease [122, 123]. Using this approach of generating neurons from presenilin-associated FAD patient’s fibroblasts, increased A...

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...senilin (PSEN) gene mutations display relatively higher Aβ42/Aβ40 ratios to thosesderived from unaffected individuals, which is a typical feature in the familial form yet with ansamplified expression =-=[88,89]-=-. Although this well-characterized phenotype can provide a comparablysuseful platform for further investigation on pathological mechanisms and drug therapeuticseffectiveness, just two disease forms ca...

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...72 [46–48] Spinal muscular atrophy SMN1, SMN2 [49, 50] Down syndrome Trisomy 21 [50, 51] Huntington disease HTT (CAG-type repetitiveDNA sequences) [52, 53] sufficient quantity or quality and this presents exciting prospects for elucidating the etiology of AD and for the development of potential therapeutics [20]. Several groups have since generated neurons from human iPSCs carrying mutations in genes encoding amyloid precursor protein (APP) and presenilin (PS), demonstrating that they recapitulate the APP processing pathway and provide an innovative approach to studying the pathogenesis of AD [11, 80, 81]. Kondo et al. derived human iPSCs from atypical earlyonset familial AD (fAD) patients with APP-E693Δ mutation showing overt early-onset symptoms of AD but lacking A...

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...cterized by being age-related [83] meaning that neurons gradually lose their function as these neurodegenerative diseases progress with age. Currently, reprogramming technology allows researchers to study the development and progression of neurodegeneration in a human system and thismay in turn enables the development of new early diagnostic technologies and improved treatment modalities. Stem Cells International 7 Table 3: In vitromodeling of neurodegenerative and neurodevelopmental disorders with hPSCs-derived neuronal lineages. Disease model Key references Alzheimer’s disease Israel et al. [84] Huntington’s disease An et al. [85]The HD iPSC Consortium [86] Amyotrophic lateral sclerosis Mitne-Neto et al. [87] Autism spectrum disorder Kim et al. [88] Schizophrenia Chiang et al. [89]Brennand et al. [90] Rett syndrome Ananiev et al. [91] Cheung et al. [92] Li et al. [93] Williams et al. [94] Fragile X syndrome Sheridan et al. [95] Bar-Nur et al. [96] Liu et al. [97] Timothy syndrome Pasca et al. [98]Krey et al. [99] Alzheimer’s disease is the most common type of agerelated dementia found in aging population and is the 6th leading cause of death in USA [100]. Clinically, the disease is ...

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...(i) DS iPSCs with three pairs of chromosomes 21 (T21-iPSCs); (ii) isogenic iPSCs from DS individuals; (iii) DS iPSCs with trisomy 21 deletion through TKNEO; (iv) DS iPSCs with trisomy 21 deletion through Xist [70, 78–80] Schizophrenia DISC1 (i) Decreased neuronal connectivity; (ii) synaptic deficits; (iii) PSD95 downregulation; (iv) fewer neurites Neurons (i) iPSCs from schizophrenia patients; (ii) SZ iPSCs with a mutation in DISC1 gene [81, 82] kinase 3 beta (GSK3B). Treatment of the neurons with ...

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...ries during differentiation. In addition, no accumulation of tau proteinwas observed in this type of FAD-derived neurons [80]. However, the PSEN1 A246E mutant was further analyzed during the differentiation and observed an increase in the ratio of A...