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induced pluripotent stem cell alzheimer's

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https://www.readbyqxmd.com/read/28912154/inhibition-of-p25-cdk5-attenuates-tauopathy-in-mouse-and-ipsc-models-of-frontotemporal-dementia
#1
Jinsoo Seo, Oleg Kritskiy, L Ashley Watson, Scarlett J Barker, Dilip Dey, Waseem K Raja, Yuan-Ta Lin, Tak Ko, Sukhee Cho, Jay Penney, M Catarina Silva, Steven D Sheridan, Diane Lucente, James F Gusella, Bradford C Dickerson, Stephen J Haggarty, Li-Huei Tsai
Increased p25, a proteolytic fragment of the regulatory subunit p35, is known to induce aberrant activity of cyclin-dependent kinase 5 (Cdk5), which is associated with neurodegenerative disorders including Alzheimer's disease (AD). Previously, we showed that replacing endogenous p35 with the non-cleavable mutant p35 (Δp35) attenuated amyloidosis and improved cognitive function in a familial AD mouse model. Here, to address the role of p25/Cdk5 in tauopathy, we generated double transgenic mice by crossing mice overexpressing mutant human tau (P301S) with Δp35KI mice...
September 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28903069/cell-reprogramming-therapeutic-potential-and-the-promise-of-rejuvenation-for-the-aging-brain
#2
REVIEW
Micaela López-León, Tiago F Outeiro, Rodolfo G Goya
Aging is associated with a progressive increase in the incidence of neurodegenerative diseases, with Alzheimer's (AD) and Parkinson's (PD) disease being the most conspicuous examples. Within this context, the absence of efficacious therapies for most age-related brain pathologies has increased the interest in regenerative medicine. In particular, cell reprogramming technologies have ushered in the era of personalized therapies that not only show a significant potential for the treatment of neurodegenerative diseases but also promise to make biological rejuvenation feasible...
September 10, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28880277/use-of-a-neonatal-rat-system-as-a-bioincubator-to-generate-adult-like-mature-cardiomyocytes-from-human-and-mouse-pluripotent-stem-cells
#3
Gun-Sik Cho, Emmanouil Tampakakis, Peter Andersen, Chulan Kwon
Pluripotent stem cells (PSCs), including induced PSCs, hold great potential for personalized disease modeling, drug testing and cell-based therapeutics. However, cells differentiated from PSCs remain immature in a dish, and thus there are serious caveats to their use in modeling adult-onset diseases such as cardiomyopathies and Alzheimer's disease. By taking advantage of knowledge gained about mammalian development and from bioinformatics analyses, we recently developed a neonatal rat system that enables maturation of PSC-derived cardiomyocytes into cardiomyocytes analogous to those seen in adult animals...
October 2017: Nature Protocols
https://www.readbyqxmd.com/read/28822354/3d-brain-organoids-derived-from-pluripotent-stem-cells-promising-experimental-models-for-brain-development-and-neurodegenerative-disorders
#4
REVIEW
Chun-Ting Lee, Raphael M Bendriem, Wells W Wu, Rong-Fong Shen
Three-dimensional (3D) brain organoids derived from human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), appear to recapitulate the brain's 3D cytoarchitectural arrangement and provide new opportunities to explore disease pathogenesis in the human brain. Human iPSC (hiPSC) reprogramming methods, combined with 3D brain organoid tools, may allow patient-derived organoids to serve as a preclinical platform to bridge the translational gap between animal models and human clinical trials...
August 20, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28805182/human-induced-pluripotent-stem-cells-as-a-research-tool-in-alzheimer-s-disease
#5
J P Robbins, J Price
Human-induced pluripotent stem cells (iPSCs) offer a novel, timely approach for investigating the aetiology of neuropsychiatric disorders. Although we are starting to gain more insight into the specific mechanisms that cause Alzheimer's disease and other forms of dementia, this has not resulted in therapies to slow the pathological processes. Animal models have been paramount in studying the neurobiological processes underlying psychiatric disorders. Nonetheless, these human conditions cannot be entirely recapitulated in rodents...
August 14, 2017: Psychological Medicine
https://www.readbyqxmd.com/read/28748763/induced-pluripotent-stem-cell-technology-a-paradigm-shift-in-medical-science-for-drug-screening-and-disease-modeling
#6
Meera Nair, Sardul Singh Sandhu, Anil Kumar Sharma
BACKGROUND: Induced Pluripotent Stem Cell (IPSC) Technology is the most advanced research as it offers an attractive alternative for establishing patient-specific IPSCs to recapitulate phenotypes of not only monogenic diseases (viz. Thalassaemia, Sickle cell anemia, Haemophilia, Tay-Sachs disease), but also late-onset polygenic diseases (viz. Parkinson's disease, Alzheimer's disease, schizophrenia). Over the hindsight, numerous studies of the past and current scientists have led to the production, maturation and understanding of induced pluripotent stem cell technology and its use in basic and clinical research...
July 27, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28696436/reduced-trpc6-mrna-levels-in-the-blood-cells-of-patients-with-alzheimer-s-disease-and-mild-cognitive-impairment
#7
R Lu, J Wang, R Tao, J Wang, T Zhu, W Guo, Y Sun, H Li, Y Gao, W Zhang, C J Fowler, Q Li, S Chen, Z Wu, C L Masters, C Zhong, N Jing, Y Wang, Y Wang
Transient receptor potential canonical 6 (TRPC6) inhibits β-amyloid (Aβ) production. Hyperforin, the TRPC6 agonist, reduces Aβ levels and improves cognitive performance in Alzheimer's disease (AD) models. However, it's unknown whether TRPC6 expression is changed in AD patients. In this case-control study, we measured TRPC6 expression levels in the peripheral blood cells of four independent AD sets from five hospitals and one mild cognitive impairment (MCI) set from a local community (229 AD, 70 MCI, 40 Parkinson disease and 359 controls from China, total n=698) using quantitative real-time PCR assay...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28674976/alzheimer-s-disease-insights-from-genetic-mouse-models-and-current-advances-in-human-ipsc-derived-neurons
#8
Anne E Harasta, Lars M Ittner
Alzheimer's disease was first described in 1906 and since then tremendous efforts have been made to fully understand the disease pathology and to find a cure for this neurodegenerative disease. The diagnosis of Alzheimer's is still difficult, especially in early stages of the disease. Current treatment of Alzheimer's only ameliorates the symptoms but fails to provide a therapy. Over the last decades, animal models have been proven valuable in elucidating insights of the pathology. In vitro models using patient-derived cells are currently emerging and hold great promise in understanding the disease pathophysiology...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28643190/mitochondrial-biogenesis-and-neural-differentiation-of-human-ipsc-is-modulated-by-idebenone-in-a-developmental-stage-dependent-manner
#9
J Augustyniak, J Lenart, M Zychowicz, P P Stepien, L Buzanska
Idebenone, the synthetic analog of coenzyme Q10 can improve electron transport in mitochondria. Therefore, it is used in the treatment of Alzheimer's disease and other cognitive impairments. However, the mechanism of its action on neurodevelopment is still to be elucidated. Here we demonstrate that the cellular response of human induced pluripotent stem cells (hiPSC) to idebenone depends on the stage of neural differentiation. When: neural stem cells (NSC), early neural progenitors (eNP) and advanced neural progenitors (NP) have been studied a significant stimulation of mitochondrial biogenesis was observed only at the eNP stage of development...
August 2017: Biogerontology
https://www.readbyqxmd.com/read/28610892/novel-human-neuronal-tau-model-exhibiting-neurofibrillary-tangles-and-transcellular-propagation
#10
Patrick Reilly, Charisse N Winston, Kelsey R Baron, Margarita Trejo, Edward M Rockenstein, Johnny C Akers, Najla Kfoury, Marc Diamond, Eliezer Masliah, Robert A Rissman, Shauna H Yuan
Tauopathies are a class of neurodegenerative diseases, including Alzheimer's disease, frontotemporal dementia and progressive supranuclear palsy, which are associated with the pathological aggregation of tau protein into neurofibrillary tangles (NFT). Studies have characterized tau as a "prion-like" protein given its ability to form distinct, stable amyloid conformations capable of transcellular and multigenerational propagation in clonal fashion. It has been proposed that progression of tauopathy could be due to the prion-like propagation of tau, suggesting the possibility that end-stage pathologies, like NFT formation, may require an instigating event such as tau seeding...
October 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28610595/stem-cell-models-of-alzheimer-s-disease-progress-and-challenges
#11
REVIEW
Charles Arber, Christopher Lovejoy, Selina Wray
A major challenge to our understanding of the molecular mechanisms of Alzheimer's disease (AD) has been the lack of physiologically relevant in vitro models which capture the precise patient genome, in the cell type of interest, with physiological expression levels of the gene(s) of interest. Induced pluripotent stem cell (iPSC) technology, together with advances in 2D and 3D neuronal differentiation, offers a unique opportunity to overcome this challenge and generate a limitless supply of human neurons for in vitro studies...
June 13, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28591569/the-alzheimer-s-disease-%C3%AE-secretase-generates-higher-42-40-ratios-for-%C3%AE-amyloid-than-for-p3-peptides
#12
Gabriele Siegel, Hermeto Gerber, Philipp Koch, Oliver Bruestle, Patrick C Fraering, Lawrence Rajendran
Alzheimer's disease is characterized by intracerebral deposition of β-amyloid (Aβ). While Aβ40 is the most abundant form, neurotoxicity is mainly mediated by Aβ42. Sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretases gives rise to full-length Aβ (Aβ1-x) and N-terminally truncated Aβ' (Aβ11-x) whereas cleavage by α- and γ-secretases leads to the shorter p3 peptides (Aβ17-x). We uncovered significantly higher ratios of 42- versus 40-ending variants for Aβ and Aβ' than for p3 secreted by mouse neurons and human induced pluripotent stem cell (iPSC)-derived neurons or produced in a cell-free γ-secretase assay with recombinant APP-CTFs...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28585382/modeling-tau-pathology-in-human-stem-cell-derived-neurons
#13
Selina Wray
Tau pathology is a defining characteristic of multiple neurodegenerative disorders including Alzheimer's disease (AD) and Frontotemporal Dementia (FTD) with tau pathology. There is strong evidence from genetics and experimental models to support a central role for tau dysfunction in neuronal death, suggesting tau is a promising therapeutic target for AD and FTD. However, the development of tau pathology can precede symptom onset by several years, so understanding the earliest molecular events in tauopathy is a priority area of research...
July 2017: Brain Pathology
https://www.readbyqxmd.com/read/28579476/modeling-neurodegenerative-diseases-with-patient-derived-induced-pluripotent-cells-possibilities-and-challenges
#14
REVIEW
Anna Poon, Yu Zhang, Abinaya Chandrasekaran, Phetcharat Phanthong, Benjamin Schmid, Troels T Nielsen, Kristine K Freude
The rising prevalence of progressive neurodegenerative diseases coupled with increasing longevity poses an economic burden at individual and societal levels. There is currently no effective cure for the majority of neurodegenerative diseases and disease-affected tissues from patients have been difficult to obtain for research and drug discovery in pre-clinical settings. While the use of animal models has contributed invaluable mechanistic insights and potential therapeutic targets, the translational value of animal models could be further enhanced when combined with in vitro models derived from patient-specific induced pluripotent stem cells (iPSCs) and isogenic controls generated using CRISPR-Cas9 mediated genome editing...
June 2, 2017: New Biotechnology
https://www.readbyqxmd.com/read/28448871/immunomodulatory-effects-of-stem-cells-therapeutic-option-for-neurodegenerative-disorders
#15
REVIEW
Martin Caprnda, Peter Kubatka, Katarina Gazdikova, Iveta Gasparova, Vanda Valentova, Nadezda Stollarova, Giampiero La Rocca, Nazarii Kobyliak, Jozef Dragasek, Ioana Mozos, Robert Prosecky, Dario Siniscalco, Dietrich Büsselberg, Luis Rodrigo, Peter Kruzliak
Stem cells have the capability of self-renewal and can differentiate into different cell types that might be used in regenerative medicine. Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) currently lack effective treatments. Although stem cell therapy is still on the way from bench to bedside, we consider that it might provide new hope for patients suffering with neurodegenerative diseases. In this article, we will give an overview of recent studies on the potential therapeutic use of mesenchymal stem cells (MSCs), neural stem cells (NSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and perinatal stem cells to neurodegenerative disorders and we will describe their immunomodulatory mechanisms of action in specific therapeutic modalities...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28444230/apoe-%C3%AE%C2%B54-%C3%AE%C2%B54-diminishes-neurotrophic-function-of-human-ipsc-derived-astrocytes
#16
Jing Zhao, Mary D Davis, Yuka A Martens, Mitsuru Shinohara, Neill R Graff-Radford, Steven G Younkin, Zbigniew K Wszolek, Takahisa Kanekiyo, Guojun Bu
The ε4 allele of the APOE gene encoding apolipoprotein E (apoE) is a strong genetic risk factor for aging-related cognitive decline as well as late-onset Alzheimer's disease (AD) compared to the common ε3 allele. In the central nervous system, apoE is produced primarily by astrocytes and functions in transporting lipids including cholesterol to support neuronal homeostasis and synaptic integrity. Although mouse models and corresponding primary cells have provided valuable tools for studying apoE isoform-dependent functions, recent studies have shown that human astrocytes have a distinct gene expression profile compare with rodent astrocytes...
July 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28413002/characterization-of-human-induced-pluripotent-stem-cell-ipsc-line-from-a-72year-old-male-patient-with-later-onset-alzheimer-s-disease
#17
Shaokun Zhang, Zhenshan Lv, Songyuan Zhang, Lidi Liu, Qiao Li, Weiquan Gong, Hui Sha, Hong Wu
Peripheral blood was collected from a clinically diagnosed 72-year old male patient with later onset Alzheimer's disease. Peripheral blood mononuclear cells (PBMCs) were reprogrammed with the Yamanaka KMOS reprogramming factors using the Sendai-virus reprogramming system. The transgene-free iPSC line showed pluripotency verified by immunofluorescent staining for pluripotency markers, and the iPSC line was able to differentiate into the 3 germ layers in vivo. The iPSC line also showed normal karyotype. This in vitro cellular model will be useful for studying the pathological mechanism of Alzheimer's disease...
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28398169/paving-the-way-toward-complex-blood-brain-barrier-models-using-pluripotent-stem-cells
#18
Karin Lauschke, Lise Frederiksen, Vanessa Jane Hall
A tissue with great need to be modeled in vitro is the blood-brain barrier (BBB). The BBB is a tight barrier that covers all blood vessels in the brain and separates the brain microenvironment from the blood system. It consists of three cell types [neurovascular unit (NVU)] that contribute to the unique tightness and selective permeability of the BBB and has been shown to be disrupted in many diseases and brain disorders, such as vascular dementia, stroke, multiple sclerosis, and Alzheimer's disease. Given the progress that pluripotent stem cells (PSCs) have made in the past two decades, it is now possible to produce many cell types from the BBB and even partially recapitulate this complex tissue in vitro...
June 15, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28334857/co-cultures-with-stem-cell-derived-human-sensory-neurons-reveal-regulators-of-peripheral-myelination
#19
Alex J Clark, Malte S Kaller, Jorge Galino, Hugh J Willison, Simon Rinaldi, David L H Bennett
See Saporta and Shy (doi:10.1093/awx048) for a scientific commentary on this article.Effective bidirectional signalling between axons and Schwann cells is essential for both the development and maintenance of peripheral nerve function. We have established conditions by which human induced pluripotent stem cell-derived sensory neurons can be cultured with rat Schwann cells, and have produced for the first time long-term and stable myelinating co-cultures with human neurons. These cultures contain the specialized domains formed by axonal interaction with myelinating Schwann cells, such as clustered voltage-gated sodium channels at the node of Ranvier and Shaker-type potassium channel (Kv1...
April 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28333144/aberrant-ipsc-derived-human-astrocytes-in-alzheimer-s-disease
#20
V C Jones, R Atkinson-Dell, A Verkhratsky, L Mohamet
The pathological potential of human astroglia in Alzheimer's disease (AD) was analysed in vitro using induced pluripotent stem cell (iPSC) technology. Here, we report development of a human iPSC-derived astrocyte model created from healthy individuals and patients with either early-onset familial AD (FAD) or the late-onset sporadic form of AD (SAD). Our chemically defined and highly efficient model provides >95% homogeneous populations of human astrocytes within 30 days of differentiation from cortical neural progenitor cells (NPCs)...
March 23, 2017: Cell Death & Disease
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