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induced pluripotent stem cell alzheimer's

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https://www.readbyqxmd.com/read/28293168/modeling-human-neurological-and-neurodegenerative-diseases-from-induced-pluripotent-stem-cells-to-neuronal-differentiation-and-its-applications-in-neurotrauma
#1
REVIEW
Hisham Bahmad, Ola Hadadeh, Farah Chamaa, Katia Cheaito, Batoul Darwish, Ahmad-Kareem Makkawi, Wassim Abou-Kheir
With the help of several inducing factors, somatic cells can be reprogrammed to become induced pluripotent stem cell (iPSCs) lines. The success is in obtaining iPSCs almost identical to embryonic stem cells (ESCs), therefore various approaches have been tested and ultimately several ones have succeeded. The importance of these cells is in how they serve as models to unveil the molecular pathways and mechanisms underlying several human diseases, and also in its potential roles in the development of regenerative medicine...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28259862/-modeling-neurological-and-psychiatric-disorders-in-vitro-using-induced-pluripotent-stem-cells-highlighting-findings-in-alzheimer-s-disease-and-schizophrenia
#2
Edit Hathy, Sara Kalman, Agota Apati, Zsofia Nemoda, Janos M Rethelyi
Over the past decade we witnessed the birth of a new scientific area that lies at the borders of developmental biology, stem cell biology, basic and clinical neuroscience. In vitro disease modeling refers to the approach that exploits the capacity of stem cells for self-renewal and pluripotency by generating specific cell types that are relevant for a given disorder. Based on this method, neurological and psychiatric disorders can be investigated by differentiating stem cells into neurons in a dish, and studying the relevant neuronal populations affected in the pathophysiology of the disorder in terms of specific cellular phenotypes...
December 2016: Neuropsychopharmacologia Hungarica
https://www.readbyqxmd.com/read/28237843/characterization-of-energy-and-neurotransmitter-metabolism-in-cortical-glutamatergic-neurons-derived-from-human-induced-pluripotent-stem-cells-a-novel-approach-to-study-metabolism-in-human-neurons
#3
Blanca I Aldana, Yu Zhang, Maria Fog Lihme, Lasse K Bak, Jørgen E Nielsen, Bjørn Holst, Poul Hyttel, Kristine K Freude, Helle S Waagepetersen
Alterations in the cellular metabolic machinery of the brain are associated with neurodegenerative disorders such as Alzheimer's disease. Novel human cellular disease models are essential in order to study underlying disease mechanisms. In the present study, we characterized major metabolic pathways in neurons derived from human induced pluripotent stem cells (hiPSC). With this aim, cultures of hiPSC-derived neurons were incubated with [U-(13)C]glucose, [U-(13)C]glutamate or [U-(13)C]glutamine. Isotopic labeling in metabolites was determined using gas chromatography coupled to mass spectrometry, and cellular amino acid content was quantified by high-performance liquid chromatography...
February 24, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28193519/thiamine-deficiency-induces-endoplasmic-reticulum-stress-and-oxidative-stress-in-human-neurons-derived-from-induced-pluripotent-stem-cells
#4
Xin Wang, Mei Xu, Jacqueline A Frank, Zun-Ji Ke, Jia Luo
Thiamine (vitamin B1) deficiency (TD) plays a major role in the etiology of Wernicke's encephalopathy (WE) which is a severe neurological disorder. TD induces selective neuronal cell death, neuroinflammation, endoplasmic reticulum (ER) stress and oxidative stress in the brain which are commonly observed in many aging-related neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and progressive supranuclear palsy (PSP). However, the underlying cellular and molecular mechanisms remain unclear...
April 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28170178/protein-induced-pluripotent-stem-cells-ameliorate-cognitive-dysfunction-and-reduce-a%C3%AE-deposition-in-a-mouse-model-of-alzheimer-s-disease
#5
Moon-Yong Cha, Yoo-Wook Kwon, Hyo-Suk Ahn, Hyobin Jeong, Yong Yook Lee, Minho Moon, Sung Hoon Baik, Dong Kyu Kim, Hyundong Song, Eugene C Yi, Daehee Hwang, Hyo-Soo Kim, Inhee Mook-Jung
Transplantation of stem cells into the brain attenuates functional deficits in the central nervous system via cell replacement, the release of specific neurotransmitters, and the production of neurotrophic factors. To identify patient-specific and safe stem cells for treating Alzheimer's disease (AD), we generated induced pluripotent stem cells (iPSCs) derived from mouse skin fibroblasts by treating protein extracts of embryonic stem cells. These reprogrammed cells were pluripotent but nontumorigenic. Here, we report that protein-iPSCs differentiated into glial cells and decreased plaque depositions in the 5XFAD transgenic AD mouse model...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28148781/the-amino-acid-metabolite-homocysteine-activates-mtorc1-to-inhibit-autophagy-and-form-abnormal-proteins-in-human-neurons-and-mice
#6
Khoosheh Khayati, Henri Antikainen, Edward M Bonder, Gregory F Weber, Warren D Kruger, Hieronim Jakubowski, Radek Dobrowolski
The molecular mechanisms leading to and responsible for age-related, sporadic Alzheimer's disease (AD) remain largely unknown. It is well documented that aging patients with elevated levels of the amino acid metabolite homocysteine (Hcy) are at high risk of developing AD. We investigated the impact of Hcy on molecular clearance pathways in mammalian cells, including in vitro cultured induced pluripotent stem cell-derived forebrain neurons and in vivo neurons in mouse brains. Exposure to Hcy resulted in up-regulation of the mechanistic target of rapamycin complex 1 (mTORC1) activity, one of the major kinases in cells that is tightly linked to anabolic and catabolic pathways...
February 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28059787/neurons-derived-from-induced-pluripotent-stem-cells-of-patients-with-down-syndrome-reproduce-early-stages-of-alzheimer-s-disease-type-pathology-in-vitro
#7
Erdem B Dashinimaev, Alexander S Artyuhov, Alexey P Bolshakov, Ekaterina A Vorotelyak, Andrey V Vasiliev
People with Down syndrome (DS) are at high risk of developing pathology similar to Alzheimer's disease (AD). Modeling of this pathology in vitro may be useful for studying this phenomenon. In this study, we analyzed three different cultures of neural cells carrying trisomy of chromosome 21, which were generated by directed differentiation from induced pluripotent stem cells (iPS cells). We report here that in vitro generated DS neural cells have abnormal metabolism of amyloid-β (Aβ) manifested by increased secretion and accumulation of Aβ granules of Aβ42 pathological isoform with upregulated expression of the APP gene...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28034781/increased-susceptibility-to-a%C3%AE-toxicity-in-neuronal-cultures-derived-from-familial-alzheimer-s-disease-psen1-a246e-induced-pluripotent-stem-cells
#8
Enrique Armijo, Cesar Gonzalez, Mohammad Shahnawaz, Andrea Flores, Brian Davis, Claudio Soto
Alzheimer's disease (AD) is the most common cause of late-life dementia and represents one of the leading causes of death worldwide. The generation of induced pluripotent stem cells (iPSC) has facilitated the production and differentiation of stem cells from patients somatic cells, offering new opportunities to model AD and other diseases in vitro. In this study, we generated iPSCs from skin fibroblasts obtained from a healthy individual, as well as sporadic (sAD) and familial AD (fAD, PSEN1-A246E mutation) patients...
February 3, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/27981499/direct-conversion-of-somatic-cells-into-induced-neurons
#9
REVIEW
Na An, Huiming Xu, Wei-Qiang Gao, Hao Yang
The progressive loss and degeneration of neurons in the central nervous system (CNS), as a result of traumas or diseases including Alzheimer's, Parkinson's, Huntington's disease, stroke, and traumatic injury to the brain and spinal cord, can usually have devastating effects on quality of life. The current strategies available for treatments are described including drug delivery, surgery, electrical stimulation, and cell-based tissue engineering approaches. However, apart from cell-based therapy, other attempts are limited in improving clinical outcomes...
December 16, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27938410/3d-culture-models-of-alzheimer-s-disease-a-road-map-to-a-cure-in-a-dish
#10
REVIEW
Se Hoon Choi, Young Hye Kim, Luisa Quinti, Rudolph E Tanzi, Doo Yeon Kim
Alzheimer's disease (AD) transgenic mice have been used as a standard AD model for basic mechanistic studies and drug discovery. These mouse models showed symbolic AD pathologies including β-amyloid (Aβ) plaques, gliosis and memory deficits but failed to fully recapitulate AD pathogenic cascades including robust phospho tau (p-tau) accumulation, clear neurofibrillary tangles (NFTs) and neurodegeneration, solely driven by familial AD (FAD) mutation(s). Recent advances in human stem cell and three-dimensional (3D) culture technologies made it possible to generate novel 3D neural cell culture models that recapitulate AD pathologies including robust Aβ deposition and Aβ-driven NFT-like tau pathology...
December 9, 2016: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/27926491/early-pathogenic-event-of-alzheimer-s-disease-documented-in-ipscs-from-patients-with-psen1-mutations
#11
Juan Yang, Hanzhi Zhao, Yu Ma, Guilai Shi, Jian Song, Yu Tang, Song Li, Ting Li, Nan Liu, Fan Tang, Junjie Gu, Lingling Zhang, Zhuohua Zhang, Xiaohui Zhang, Ying Jin, Weidong Le
Alzheimer's disease (AD) is the most common age-related dementia characterized by progressive neuronal loss. However, the molecular mechanisms for the neuronal loss is still debated. Here, we used induced pluripotent stem cells (iPSCs) derived from somatic cells of familial AD patients carrying PSEN1 mutations to study the early pathogenic event of AD. We found that premature neuronal differentiation with decreased proliferation and increased apoptosis occured in AD-iPSC-derived neural progenitor cells (AD-NPCs) once neuronal differentiation was initiated, together with higher levels of Aβ42 and phosphorylated tau...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27897204/human-mitochondrial-transcriptional-factor-a-breaks-the-mitochondria-mediated-vicious-cycle-in-alzheimer-s-disease
#12
Sugako Oka, Julio Leon, Kunihiko Sakumi, Tomomi Ide, Dongchon Kang, Frank M LaFerla, Yusaku Nakabeppu
In the mitochondria-mediated vicious cycle of Alzheimer's disease (AD), intracellular amyloid β (Aβ) induces mitochondrial dysfunction and reactive oxygen species, which further accelerate Aβ accumulation. This vicious cycle is thought to play a pivotal role in the development of AD, although the molecular mechanism remains unclear. Here, we examined the effects of human mitochondrial transcriptional factor A (hTFAM) on the pathology of a mouse model of AD (3xTg-AD), because TFAM is known to protect mitochondria from oxidative stress through maintenance of mitochondrial DNA (mtDNA)...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27879212/generation-of-a-gene-corrected-isogenic-control-cell-line-from-an-alzheimer-s-disease-patient-ipsc-line-carrying-a-a79v-mutation-in-psen1
#13
Carlota Pires, Benjamin Schmid, Carina Petræus, Anna Poon, Natakarn Nimsanor, Troels T Nielsen, Gunhild Waldemar, Lena E Hjermind, Jørgen E Nielsen, Poul Hyttel, Kristine K Freude
Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease causing neural cell degeneration and brain atrophy and is considered to be the most common form of dementia. We previously generated an induced pluripotent stem cell (iPSC) line from an AD patient carrying an A79V mutation in PSEN1 as an in vitro disease model. Here we generated a gene-corrected version from this hiPSC line by substituting the point mutation with the wild-type sequence. The reported A79V-GC-iPSCs line is a very useful resource in combination with the A79V-iPSC line in order to study pathological cellular phenotypes related to this particular mutation...
September 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27853631/stepping-back-to-move-forward-a-current-review-of-ipscs-in-the-fight-against-alzheimer-s-disease
#14
REVIEW
Aditya Devineni, Scarlett Tohme, Michael T Kody, R Adams Cowley, Brent T Harris
The successful generation of the first iPSCs about ten years ago has provided deeper insight into previously unknown disease mechanisms and therapeutic opportunities for many diseases. In particular, iPSCs are becoming an important tool in advancing modeling and therapeutic intervention for Alzheimer's disease. In this manuscript, we assess the research climate surrounding the application of iPSCs to familial and sporadic Alzheimer's disease, including the generation and isolation of individualized neural stem cells, the introduction of neural stem cell transplants using iPSCs, and an estimation of the potential use of iPSCs as research models for Alzheimer's treatments and therapies...
2016: American Journal of Stem Cells
https://www.readbyqxmd.com/read/27819315/sustained-synchronized-neuronal-network-activity-in-a-human-astrocyte-co-culture-system
#15
Jacobine Kuijlaars, Tutu Oyelami, Annick Diels, Jutta Rohrbacher, Sofie Versweyveld, Giulia Meneghello, Marianne Tuefferd, Peter Verstraelen, Jan R Detrez, Marlies Verschuuren, Winnok H De Vos, Theo Meert, Pieter J Peeters, Miroslav Cik, Rony Nuydens, Bert Brône, An Verheyen
Impaired neuronal network function is a hallmark of neurodevelopmental and neurodegenerative disorders such as autism, schizophrenia, and Alzheimer's disease and is typically studied using genetically modified cellular and animal models. Weak predictive capacity and poor translational value of these models urge for better human derived in vitro models. The implementation of human induced pluripotent stem cells (hiPSCs) allows studying pathologies in differentiated disease-relevant and patient-derived neuronal cells...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27789410/lymphoblast-derived-integration-free-ipsc-lines-from-a-female-and-male-alzheimer-s-disease-patient-expressing-different-copy-numbers-of-a-coding-cnv-in-the-alzheimer-risk-gene-cr1
#16
Friederike Schröter, Kristel Sleegers, Caroline Van Cauwenberghe, Martina Bohndorf, Wasco Wruck, Christine Van Broeckhoven, James Adjaye
Human lymphoblast cells from a female and male patient diagnosed with Alzheimer's disease (AD) with different genotypes of a functional copy number variation (CNV) in the AD risk gene CR1 were used to generate integration-free induced pluripotent stem cells (iPSCs) employing episomal plasmids expressing OCT4, SOX2, NANOG, LIN28, c-MYC and L-MYC. The iPSCs retained the CR1 CNV, and comparative transcriptome analyses with the human embryonic stem cell line H1 revealed a Pearson correlation of 0.956 for AD1-CR10 and 0...
October 19, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27789408/lymphoblast-derived-integration-free-ips-cell-line-from-a-female-67-year-old-alzheimer-s-disease-patient-with-trem2-r47h-missense-mutation
#17
Friederike Schröter, Kristel Sleegers, Elise Cuyvers, Martina Bohndorf, Wasco Wruck, Christine Van Broeckhoven, James Adjaye
Human lymphoblast cells from a female patient diagnosed with Alzheimer's disease (AD) possessing the missense mutation TREM2 p.R47H were used to generate integration-free induced pluripotent stem cells (iPSCs) employing episomal plasmids expressing OCT4, SOX2, NANOG, LIN28, c-MYC and L-MYC. The iPSCs retained the TREM2 mutation, and were defined as pluripotent based on (i) expression of pluripotent-associated markers, (ii) embryoid body-based differentiation into cell types representative of the three germ layers and (iii) the similarity between the transcriptomes of the iPSC line and the human embryonic stem cell line H1 with a Pearson correlation of 0...
October 20, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27789396/derivation-of-induced-pluripotent-stem-cells-from-a-familial-alzheimer-s-disease-patient-carrying-the-l282f-mutation-in-presenilin-1
#18
Anna Poon, Tong Li, Carlota Pires, Troels T Nielsen, Jørgen E Nielsen, Bjørn Holst, Andras Dinnyes, Poul Hyttel, Kristine K Freude
Mutations in presenilin 1 (PSEN1) lead to the most aggressive form of familial Alzheimer's disease (AD). Human induced pluripotent stem cells (hiPSCs) derived from AD patients can be differentiated and used for disease modeling. Here, we derived hiPSC from skin fibroblasts obtained from an AD patient carrying a L282F mutation in PSEN1. We transfected skin fibroblasts with episomal iPSC reprogramming vectors targeting human OCT4, SOX2, L-MYC, KLF4, NANOG, LIN28, and short hairpin RNA against TP53. Our hiPSC line, L282F-hiPSC, displayed typical stem cell characteristics with consistent expression of pluripotency genes and the ability to differentiation into the three germ layers...
September 28, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27789395/generation-of-a-gene-corrected-isogenic-control-hipsc-line-derived-from-a-familial-alzheimer-s-disease-patient-carrying-a-l150p-mutation-in-presenilin-1
#19
Anna Poon, Benjamin Schmid, Carlota Pires, Troels T Nielsen, Lena E Hjermind, Jørgen E Nielsen, Bjørn Holst, Poul Hyttel, Kristine K Freude
Mutations in the presenilin 1 (PSEN1) gene lead to the most aggressive form of familial Alzheimer's disease (AD). Human induced pluripotent stem cells (hiPSCs) derived from AD patients and subsequently differentiated can be used for disease modeling. We have previously generated a hiPSC line from a familial AD patient carrying a L150P point mutation in PSEN1. Here we used CRISPR/Cas9 gene editing to correct for the single base pair mutation. This gene-corrected line, L150P-GC-hiPSC, serves as an isogenic control to the mutant line for future investigation of mechanisms and cellular phenotypes altered by this specific PSEN1 mutation...
September 24, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27762639/stem-cells-for-modeling-and-therapy-of-parkinson-s-disease
#20
Qingxi Zhang, Wanling Chen, Sheng Tan, Tongxiang Lin
Parkinson's disease (PD) is the second most frequent neurodegenerative disease after Alzheimer's disease, which is characterized by a low level of dopamine being expressing in the striatum and a deterioration of dopaminergic neurons (DAn) in the substantia nigra pars compacta. Generation of PD-derived DAn, including differentiation of human embryonic stem cells, human neural stem cells, human-induced pluripotent stem cells, and direct reprogramming, provides an ideal tool to model PD, creating the possibility of mimicking key essential pathological processes and charactering single-cell changes in vitro...
January 2017: Human Gene Therapy
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