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induced pluripotent stem cell alzheimer's

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https://www.readbyqxmd.com/read/29788997/2d-versus-3d-human-induced-pluripotent-stem-cell-derived-cultures-for-neurodegenerative-disease-modelling
#1
REVIEW
Eduarda G Z Centeno, Helena Cimarosti, Angela Bithell
Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results...
May 22, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29730992/a-new-tao-kinase-inhibitor-reduces-tau-phosphorylation-at-sites-associated-with-neurodegeneration-in-human-tauopathies
#2
Caterina Giacomini, Chuay-Yeng Koo, Natalia Yankova, Ignatius A Tavares, Selina Wray, Wendy Noble, Diane P Hanger, Jonathan D H Morris
In Alzheimer's disease (AD) and related tauopathies, the microtubule-associated protein tau is highly phosphorylated and aggregates to form neurofibrillary tangles that are characteristic of these neurodegenerative diseases. Our previous work has demonstrated that the thousand-and-one amino acid kinases (TAOKs) 1 and 2 phosphorylate tau on more than 40 residues in vitro. Here we show that TAOKs are phosphorylated and active in AD brain sections displaying mild (Braak stage II), intermediate (Braak stage IV) and advanced (Braak stage VI) tau pathology and that active TAOKs co-localise with both pre-tangle and tangle structures...
May 7, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29709615/common-proteomic-profiles-of-induced-pluripotent-stem-cell-derived-three-dimensional-neurons-and-brain-tissue-from-alzheimer-patients
#3
Mei Chen, Han-Kyu Lee, Lauren Moo, Eugene Hanlon, Thor Stein, Weiming Xia
We established a unique platform for proteomic analysis of cultured three-dimensional (3D) neurons and brain tissue from Alzheimer's disease (AD) patients. We collected peripheral blood mononuclear cells (PBMC), converted PBMC to induced pluripotent stem cell (iPSC) lines, and differentiated the iPSC into human 3D neuro-spheroids. The postmortem brain tissue from the superior frontal cortex, inferior frontal cortex and cerebellum area of the AD patients was compared to the same regions from the control subjects...
April 27, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29669557/discovery-biology-of-neuropsychiatric-syndromes-dbns-a-center-for-integrating-clinical-medicine-and-basic-science
#4
Biju Viswanath, Naren P Rao, Janardhanan C Narayanaswamy, Palanimuthu T Sivakumar, Arun Kandasamy, Muralidharan Kesavan, Urvakhsh Meherwan Mehta, Ganesan Venkatasubramanian, John P John, Odity Mukherjee, Meera Purushottam, Ramakrishnan Kannan, Bhupesh Mehta, Thennarasu Kandavel, B Binukumar, Jitender Saini, Deepak Jayarajan, A Shyamsundar, Sydney Moirangthem, K G Vijay Kumar, Jagadisha Thirthalli, Prabha S Chandra, Bangalore N Gangadhar, Pratima Murthy, Mitradas M Panicker, Upinder S Bhalla, Sumantra Chattarji, Vivek Benegal, Mathew Varghese, Janardhan Y C Reddy, Padinjat Raghu, Mahendra Rao, Sanjeev Jain
BACKGROUND: There is emerging evidence that there are shared genetic, environmental and developmental risk factors in psychiatry, that cut across traditional diagnostic boundaries. With this background, the Discovery biology of neuropsychiatric syndromes (DBNS) proposes to recruit patients from five different syndromes (schizophrenia, bipolar disorder, obsessive compulsive disorder, Alzheimer's dementia and substance use disorders), identify those with multiple affected relatives, and invite these families to participate in this study...
April 18, 2018: BMC Psychiatry
https://www.readbyqxmd.com/read/29607920/nobiletin-reduces-intracellular-and-extracellular-%C3%AE-amyloid-in-ips-cell-derived-alzheimer-s-disease-model-neurons
#5
Junko Kimura, Kosuke Shimizu, Koji Kajima, Akihito Yokosuka, Yoshihiro Mimaki, Naoto Oku, Yasushi Ohizumi
Alzheimer's disease (AD) is the most common cause of dementia, with progressive memory impairment. Recently, neprilysin, a β-amyloid (Aβ)-degrading enzyme has become featured as a drug target for AD. Previously, we identified nobiletin from citrus peels as a natural compound possessing anti-dementia activity. In addition, we demonstrated that nobiletin improved memory in memory-impaired animals and, further, that Aβ levels were markedly decreased in the brains of these animals. We demonstrated in vitro that nobiletin up-regulates neprilysin expression and activity in human neuroblastoma cells...
2018: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29602048/lymphoblast-derived-integration-free-ipsc-line-ad-trem2-1-from-a-67year-old-alzheimer-s-disease-patient-expressing-the-trem2-p-r47h-variant
#6
Soraia Martins, Hatice Yigit, Martina Bohndorf, Nina Graffmann, Aurelian Robert Fiszl, Wasco Wruck, Kristel Sleegers, Christine Van Broeckhoven, James Adjaye
Human lymphoblast cells from a male diagnosed with Alzheimer's disease (AD) expressing the TREM2 p.R47H variant were used to generate integration-free induced pluripotent stem cells (iPSCs) by over-expressing episomal-based plasmids harbouring OCT4, SOX2, NANOG, LIN28, c-MYC and L-MYC. AD-TREM2-1 was defined as pluripotent based on (i) expression of pluripotency-associated markers (ii) embryoid body-based differentiation into cell types representative of the three germ layers and (iii) the similarity between the transcriptome of the iPSC line and the human embryonic stem cell line H1 with a Pearson correlation of 0...
March 20, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29566794/tau-kinetics-in-neurons-and-the-human-central-nervous-system
#7
Chihiro Sato, Nicolas R Barthélemy, Kwasi G Mawuenyega, Bruce W Patterson, Brian A Gordon, Jennifer Jockel-Balsarotti, Melissa Sullivan, Matthew J Crisp, Tom Kasten, Kristopher M Kirmess, Nicholas M Kanaan, Kevin E Yarasheski, Alaina Baker-Nigh, Tammie L S Benzinger, Timothy M Miller, Celeste M Karch, Randall J Bateman
We developed stable isotope labeling and mass spectrometry approaches to measure the kinetics of multiple isoforms and fragments of tau in the human central nervous system (CNS) and in human induced pluripotent stem cell (iPSC)-derived neurons. Newly synthesized tau is truncated and released from human neurons in 3 days. Although most tau proteins have similar turnover, 4R tau isoforms and phosphorylated forms of tau exhibit faster turnover rates, suggesting unique processing of these forms that may have independent biological activities...
March 21, 2018: Neuron
https://www.readbyqxmd.com/read/29504531/induction-of-amyloid-%C3%AE-42-production-by-fipronil-and-other-pyrazole-insecticides
#8
Morgane Cam, Emilie Durieu, Marion Bodin, Antigoni Manousopoulou, Svenja Koslowski, Natalia Vasylieva, Bogdan Barnych, Bruce D Hammock, Bettina Bohl, Philipp Koch, Chiori Omori, Kazuo Yamamoto, Saori Hata, Toshiharu Suzuki, Frank Karg, Patrick Gizzi, Vesna Erakovic Haber, Vlatka Bencetic Mihaljevic, Branka Tavcar, Erik Portelius, Josef Pannee, Kaj Blennow, Henrik Zetterberg, Spiros D Garbis, Pierrick Auvray, Hermeto Gerber, Jeremy Fraering, Patrick C Fraering, Laurent Meijer
Generation of amyloid-β peptides (Aβs) by proteolytic cleavage of the amyloid-β protein precursor (AβPP), especially increased production of Aβ42/Aβ43 over Aβ40, and their aggregation as oligomers and plaques, represent a characteristic feature of Alzheimer's disease (AD). In familial AD (FAD), altered Aβ production originates from specific mutations of AβPP or presenilins 1/2 (PS1/PS2), the catalytic subunits of γ-secretase. In sporadic AD, the origin of altered production of Aβs remains unknown...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29495441/detection-of-aggregation-competent-tau-in-neuron-derived-extracellular-vesicles
#9
Francesc X Guix, Grant T Corbett, Diana J Cha, Maja Mustapic, Wen Liu, David Mengel, Zhicheng Chen, Elena Aikawa, Tracy Young-Pearse, Dimitrios Kapogiannis, Dennis J Selkoe, Dominic M Walsh
Progressive cerebral accumulation of tau aggregates is a defining feature of Alzheimer's disease (AD). A popular theory that seeks to explain the apparent spread of neurofibrillary tangle pathology proposes that aggregated tau is passed from neuron to neuron. Such a templated seeding process requires that the transferred tau contains the microtubule binding repeat domains that are necessary for aggregation. While it is not clear how a protein such as tau can move from cell to cell, previous reports have suggested that this may involve extracellular vesicles (EVs)...
February 27, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29479303/representing-diversity-in-the-dish-using-patient-derived-in-vitro-models-to-recreate-the-heterogeneity-of-neurological-disease
#10
REVIEW
Layla T Ghaffari, Alexander Starr, Andrew T Nelson, Rita Sattler
Neurological diseases, including dementias such as Alzheimer's disease (AD) and fronto-temporal dementia (FTD) and degenerative motor neuron diseases such as amyotrophic lateral sclerosis (ALS), are responsible for an increasing fraction of worldwide fatalities. Researching these heterogeneous diseases requires models that endogenously express the full array of genetic and epigenetic factors which may influence disease development in both familial and sporadic patients. Here, we discuss the two primary methods of developing patient-derived neurons and glia to model neurodegenerative disease: reprogramming somatic cells into induced pluripotent stem cells (iPSCs), which are differentiated into neurons or glial cells, or directly converting (DC) somatic cells into neurons (iNeurons) or glial cells...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29474672/leptomeninges-derived-induced-pluripotent-stem-cells-and-directly-converted-neurons-from-autopsy-cases-with-varying-neuropathologic-backgrounds
#11
Shannon E Rose, Harald Frankowski, Allison Knupp, Bonnie J Berry, Refugio Martinez, Stephanie Q Dinh, Lauren T Bruner, Sherry L Willis, Paul K Crane, Eric B Larson, Thomas Grabowski, Martin Darvas, C Dirk Keene, Jessica E Young
Patient-specific stem cell technology from skin and other biopsy sources has transformed in vitro models of neurodegenerative disease, permitting interrogation of the effects of complex human genetics on neurotoxicity. However, the neuropathologic changes that underlie cognitive and behavioral phenotypes can only be determined at autopsy. To better correlate the biology of derived neurons with age-related and neurodegenerative changes, we generated leptomeningeal cell lines from well-characterized research subjects that have undergone comprehensive postmortem neuropathologic examinations...
May 1, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29445107/progesterone-receptor-membrane-component-1-suppresses-the-p53-and-wnt-%C3%AE-catenin-pathways-to-promote-human-pluripotent-stem-cell-self-renewal
#12
Ji Yea Kim, So Young Kim, Hong Seo Choi, Min Kyu Kim, Hyun Min Lee, Young-Joo Jang, Chun Jeih Ryu
Progesterone receptor membrane component 1 (PGRMC1) is a multifunctional heme-binding protein involved in various diseases, including cancers and Alzheimer's disease. Previously, we generated two monoclonal antibodies (MAbs) 108-B6 and 4A68 against surface molecules on human pluripotent stem cells (hPSCs). Here we show that PGRMC1 is the target antigen of both MAbs, and is predominantly expressed on hPSCs and some cancer cells. PGRMC1 is rapidly downregulated during early differentiation of hPSCs. Although PGRMC1 knockdown leads to a spread-out morphology and impaired self-renewal in hPSCs, PGRMC1 knockdown hPSCs do not show apoptosis and autophagy...
February 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29439343/overactive-brca1-affects-presenilin-1-in-induced-pluripotent-stem-cell-derived-neurons-in-alzheimer-s-disease
#13
Michalina Wezyk, Aleksandra Szybinska, Joanna Wojsiat, Marcelina Szczerba, Kelly Day, Harriet Ronnholm, Malin Kele, Mariusz Berdynski, Beata Peplonska, Jakub Piotr Fichna, Jan Ilkowski, Maria Styczynska, Anna Barczak, Marzena Zboch, Anna Filipek-Gliszczynska, Krzysztof Bojakowski, Magdalena Skrzypczak, Krzysztof Ginalski, Michal Kabza, Izabela Makalowska, Maria Barcikowska-Kotowicz, Urszula Wojda, Anna Falk, Cezary Zekanowski
 The BRCA1 protein, one of the major players responsible for DNA damage response has recently been linked to Alzheimer's disease (AD). Using primary fibroblasts and neurons reprogrammed from induced pluripotent stem cells (iPSC) derived from familial AD (FAD) patients, we studied the role of the BRCA1 protein underlying molecular neurodegeneration. By whole-transcriptome approach, we have found wide range of disturbances in cell cycle and DNA damage response in FAD fibroblasts. This was manifested by significantly increased content of BRCA1 phosphorylated on Ser1524 and abnormal ubiquitination and subcellular distribution of presenilin 1 (PS1)...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29435942/identification-and-isolation-of-novel-sugar-like-rna-protecting-materials-glycylglycerins-from-pluripotent-stem-cells
#14
Shi-Lung Lin
Pluripotent stem cells are a resourceful treasure box for regenerative medicine. They contain a large variety of novel materials useful for designing and developing new medicines and therapies directed against many aging-associated degenerative disorders, including Alzheimer's disease, Parkinson's disease, stroke, diabetes, osteoporosis, and cancers. Currently, identification of these novel stem cell-specific materials is one of major breakthroughs in the field of stem cell research. Particularly, since the discovery of induced pluripotent stem cells (iPSC) in year 2006, the methods of iPSC derivation further provide an unlimited resource for screening, isolating, and even producing theses novel stem cell-specific materials in vitro...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29414602/oxidative-stress-and-altered-mitochondrial-protein-expression-in-the-absence-of-amyloid-%C3%AE-and-tau-pathology-in-ipsc-derived-neurons-from-sporadic-alzheimer-s-disease-patients
#15
Julian H Birnbaum, Debora Wanner, Anton F Gietl, Antje Saake, Thomas M Kündig, Christoph Hock, Roger M Nitsch, Christian Tackenberg
Mitochondrial dysfunction is a prominent feature of Alzheimer's disease (AD) and increased production of reactive oxygen species (ROS) has been described in postmortem brain samples and animal models. However, these observations were made at a late stage of disease and the inability to examine an early, presymptomatic phase in human neurons impeded our understanding of cause or consequence of mitochondrial dysfunction in AD. We used human induced pluripotent stem cell-derived neuronal cells (iN cells) from sporadic AD (SAD) patients and healthy control subjects (HCS) to show aberrant mitochondrial function in patient-derived cells...
March 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29402979/human-neurospheroid-arrays-for-in-vitro-studies-of-alzheimer-s-disease
#16
Mehdi Jorfi, Carla D'Avanzo, Rudolph E Tanzi, Doo Yeon Kim, Daniel Irimia
Neurospheroids are commonly used for in vitro disease modeling and drug screening. However, the heterogeneity in size of the neurospheroids mixtures available through current methods limits their utility when employed for basic mechanistic studies of neurodegenerative diseases or screening for new interventions. Here, we generate neurospheroids from immortalized neural progenitor cells and human induced pluripotent stem cells that are uniform in size, into large-scale arrays. In proof of concept experiments, we validate the neurospheroids array as a sensitive and robust tool for screening compounds over extended time...
February 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29361890/modeling-neurodegenerative-microenvironment-using-cortical-organoids-derived-from-human-stem-cells
#17
Yuanwei Yan, Liqing Song, Julie Bejoy, Jing Zhao, Takahisa Kanekiyo, Guojun Bu, Yi Zhou, Yan Li
Alzheimer's disease (AD) is one of the most common neurodegenerative disorders and causes cognitive impairment and memory deficits of the patients. The mechanism of AD is not well known, due to lack of human brain models. Recently, mini-brain tissues called organoids have been derived from human induced pluripotent stem cells (hiPSCs) for modeling human brain development and neurological diseases. Thus, the objective of this research is to model and characterize neural degeneration microenvironment using three-dimensional (3D) forebrain cortical organoids derived from hiPSCs and study the response to the drug treatment...
February 27, 2018: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/29328972/establishment-of-tusmi003-a-an-induced-pluripotent-stem-cell-ipsc-line-from-a-62-year-old-chinese-han-patient-with-alzheimer-s-disease-with-apoe3-4-genetic-background
#18
Ying Wang, Hongxiang Yu, Yue Zhang, Jing Zhang, Keni Chen, Heng Sun, Shulin Meng, Gang Li, Ying Lei, Jian Zhao
A 62-year old Chinese Han Alzheimer's disease (AD) female patient with ApoE3/4 genetic background donated her Peripheral blood mononuclear cells (PBMC). The non-integrating episomal vector system was used to reprogrammed PBMCs with the human OKSM transcription factors. The pluripotency of transgene-free iPSCs was confirmed by immunocytochemistry for pluripotency markers and by the ability of the iPSCs to differentiate spontaneously into 3 germ layers in vitro. In addition, the iPSC line displayed a normal karyotype...
March 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29304399/establishment-of-induced-pluripotent-stem-cell-line-zzui009-a-from-an-alzheimer-s-disease-patient-carrying-a-psen1-gene-mutation
#19
Yanlin Wang, Na Jing, Linlin Su, Changhe Shi, Pei Zhang, Zhilei Wang, Huifang Sun, Jing Yang, Yutao Liu, Xuejun Wen, Jin Zhang, Shoutao Zhang, Yuming Xu
Skin fibroblasts were obtained from a 42-year-old Alzheimer's disease (AD) patient carrying mutations in the PSEN1 gene. An iPSC line was successfully established using the Sendai-virus (SeV) delivery system. The patient-specific iPSCs were free of genomically integrated reprogramming genes, had the specific mutation, expressed the expected pluripotency markers, and had the potential to differentiate into cells of all three germ layers. Our model might offer a robust platform for further study of the pathomechanism of this disease as well as drug testing and gene therapy studies...
March 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29246571/generation-and-characterization-of-human-induced-pluripotent-stem-cell-hipsc-lines-from-an-alzheimer-s-disease-asui003-a-and-non-demented-control-asui004-a-patient-homozygous-for-the-apolipoprotein-e4-apoe4-risk-variant
#20
Nicholas Brookhouser, Ping Zhang, Richard Caselli, Jean J Kim, David A Brafman
Although the majority of late-onset Alzheimer's disease (AD) patients are labeled sporadic, multiple genetic risk variants have been identified, the most powerful and prevalent of which is the e4 variant of the Apolipoprotein E (APOE) gene. Here, we generated human induced pluripotent stem cell (hiPSC) lines from the peripheral blood mononuclear cells (PBMCs) of a clinically diagnosed AD patient [ASUi003-A] and a non-demented control (NDC) patient [ASUi004-A] homozygous for the APOE4 risk allele. These hiPSCs maintained their original genotype, expressed pluripotency markers, exhibited a normal karyotype, and retained the ability to differentiate into cells representative of the three germ layers...
December 2017: Stem Cell Research
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