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Parkinson disease and stem cell

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https://www.readbyqxmd.com/read/28917552/crispr-correction-of-the-prkag2-gene-mutation-in-the-patient-s-ipsc-derived-cardiomyocytes-eliminates-the-electrophysiological-and-structural-abnormalities
#1
Ronen Ben Jehuda, Binyamin Eisen, Yuval Shemer, Lucy N Mekies, Agnes Szantai, Irina Reiter, Huanhuan Cui, Kaomei Guan, Shiraz Haron-Khun, Dov Freimark, Silke R Sperling, Mihaela Gherghiceanu, Michael Arad, Ofer Binah
BACKGROUND: Mutations in the PRKAG2 gene encoding the γ-subunit of adenosine monophosphate-kinase (AMPK) cause hypertrophic cardiomyopathy (HCM) and familial-Wolff-Parkinson-White syndrome (WPW). Patients carrying the R302Q mutation in PRKAG2 present sinus bradycardia, escape rhythms, ventricular pre-excitation, supraventricular tachycardia and atrioventricular block. This mutation affects AMPK activity and increases glycogen storage in cardiomyocytes. The link between glycogen storage, WPW, HCM and arrhythmias remains unknown...
September 13, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
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/28901191/hypoxic-culture-promotes-dopaminergic-neuronal-differentiation-of-nasal-olfactory-mucosa-mesenchymal-stem-cells-via-upregulation-of-hypoxia-inducible-factor-1%C3%AE
#3
Yi Zhuo, Lei Wang, Lite Ge, Xuan Li, Da Duan, Xiaohua Teng, Miao Jiang, Kai Liu, Ting Yuan, Pei Wu, Hao Wang, Yujia Deng, Huali Xie, Ping Chen, Ying Xia, Ming Lu
Olfactory mucosa mesenchymal stem cells (OM-MSCs) display significant clonogenic activity and may be easily propagated for Parkinson's disease therapies. Methods of inducing OM-MSCs to differentiate into dopaminergic (DAergic) neurons using olfactory ensheathing cells (OECs) are thus an attractive topic of research. We designed a hypoxic induction protocol to generate DAergic neurons from OM-MSCs using a physiological oxygen (O2) level of 3% and OEC-conditioned medium (OCM; HI group). The normal induction (NI) group was cultured in O2 at ambient air level (21%)...
August 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28888991/lrrk2-functions-as-a-scaffolding-kinase-of-ask1-mediated-neuronal-cell-death
#4
Ji-Hye Yoon, Jung-Soon Mo, Mi-Yeon Kim, Eun-Jung Ann, Ji-Seon Ahn, Eun-Hye Jo, Hye-Jin Lee, Young Chul Lee, Wongi Seol, Sergiy M Yarmoluk, Thomas Gasser, Philipp J Kahle, Guang-Hui Liu, Juan Carlos Izpisua Belmonte, Hee-Sae Park
Leucine-rich repeat kinase 2 (LRRK2), a multi-domain protein, is a key causative factor in Parkinson's disease (PD). Identification of novel substrates and the molecular mechanisms underlying the effects of LRRK2 are essential for understanding the pathogenesis of PD. In this study, we showed that LRRK2 played an important role in neuronal cell death by directly phosphorylating and activating apoptosis signal-regulating kinase 1 (ASK1). LRRK2 phosphorylated ASK1 at Thr832 that is adjacent to Thr845, which serves as an autophosphorylation site...
September 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28887978/neuro-differentiated-ntera2-cancer-stem-cells-encapsulated-in-alginate-beads-first-evidence-of-biological-functionality
#5
Ilaria Cacciotti, Claudia Ceci, Alessandra Bianco, Giuseppa Pistritto
The present communication investigates an application of alginate encapsulation technology to the differentiation of the embryonic cancer stem NTera2 cells (NT2) into dopamine-producing cells. The encapsulation of cells in polymeric beads allows their immune isolation and makes them eligible for transplantation, thus representing a promising biotech tool for the delivery of biologically active compounds to the brain. The polysaccharide alginate is one of the most commonly used material for this procedure since it is well tolerated by various tissues, including the brain...
December 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28867345/a-pitx3-egfp-reporter-line-reveals-connectivity-of-dopamine-and-non-dopamine-neuronal-subtypes-in-grafts-generated-from-human-embryonic-stem-cells
#6
Jonathan C Niclis, Carlos W Gantner, Cameron P J Hunt, Jessica A Kauhausen, Jennifer C Durnall, John M Haynes, Colin W Pouton, Clare L Parish, Lachlan H Thompson
Development of safe and effective stem cell-based therapies for brain repair requires an in-depth understanding of the in vivo properties of neural grafts generated from human stem cells. Replacing dopamine neurons in Parkinson's disease remains one of the most anticipated applications. Here, we have used a human PITX3-EGFP embryonic stem cell line to characterize the connectivity of stem cell-derived midbrain dopamine neurons in the dopamine-depleted host brain with an unprecedented level of specificity. The results show that the major A9 and A10 subclasses of implanted dopamine neurons innervate multiple, developmentally appropriate host targets but also that the majority of graft-derived connectivity is non-dopaminergic...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28861160/long-nonding-rna-uca1-regulates-neural-stem-cell-differentiation-by-controlling-mir-1-hes1-expression
#7
Jiaolin Zheng, Dan Yi, Yu Liu, Mingqiu Wang, Yulan Zhu, Huaizhang Shi
Neural stem cells are able to self-renew and generate glial and neuronal lineages. Neural stem cell may serve as therapeutic method for neurological disorders including spinal cord injuries, Parkinson's disease, Huntington's disease and Alzheimer's disease. Long noncoding RNAs (lncRNAs) are longer than 200 nucleotides with limited protein-coding capacity. Recent studies have demonstreated that lncRNAs play an important role in several cellular processes including cell differentiation, cell development, proliferation, apoptosis, invasion and migration...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28858313/human-ips-cell-derived-dopaminergic-neurons-function-in-a-primate-parkinson-s-disease-model
#8
Tetsuhiro Kikuchi, Asuka Morizane, Daisuke Doi, Hiroaki Magotani, Hirotaka Onoe, Takuya Hayashi, Hiroshi Mizuma, Sayuki Takara, Ryosuke Takahashi, Haruhisa Inoue, Satoshi Morita, Michio Yamamoto, Keisuke Okita, Masato Nakagawa, Malin Parmar, Jun Takahashi
Induced pluripotent stem cells (iPS cells) are a promising source for a cell-based therapy to treat Parkinson's disease (PD), in which midbrain dopaminergic neurons progressively degenerate. However, long-term analysis of human iPS cell-derived dopaminergic neurons in primate PD models has never been performed to our knowledge. Here we show that human iPS cell-derived dopaminergic progenitor cells survived and functioned as midbrain dopaminergic neurons in a primate model of PD (Macaca fascicularis) treated with the neurotoxin MPTP...
August 30, 2017: Nature
https://www.readbyqxmd.com/read/28852404/umbilical-cord-an-unlimited-source-of-cells-differentiable-towards-dopaminergic-neurons
#9
REVIEW
Mahdi Eskandarian Boroujeni, Mossa Gardaneh
Cell replacement therapy utilizing mesenchymal stem cells as its main resource holds great promise for ultimate treatment of human neurological disorders. Parkinson's disease (PD) is a common, chronic neurodegenerative disorder hallmarked by localized degeneration of a specific set of dopaminergic neurons within a midbrain sub-region. The specific cell type and confined location of degenerating neurons make cell replacement therapy ideal for PD treatment since it mainly requires replenishment of lost dopaminergic neurons with fresh and functional ones...
July 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28831020/niche-derived-laminin-511-promotes-midbrain-dopaminergic-neuron-survival-and-differentiation-through-yap
#10
Dawei Zhang, Shanzheng Yang, Enrique M Toledo, Daniel Gyllborg, Carmen Saltó, J Carlos Villaescusa, Ernest Arenas
Parkinson's disease (PD) is a neurodegenerative disorder in which the loss of dopaminergic neurons in the midbrain (mDA neurons) causes progressive loss of motor control and function. Using embryonic and mDA neurons, midbrain tissue from mice, and differentiated human neural stem cells, we investigated the mechanisms controlling the survival of mDA neurons. We found that the extracellular matrix protein laminin-511 (LM511) promoted the survival and differentiation of mDA neurons. LM511 bound to integrin α3β1 and activated the transcriptional cofactor YAP...
August 22, 2017: Science Signaling
https://www.readbyqxmd.com/read/28827786/excess-%C3%AE-synuclein-compromises-phagocytosis-in-ipsc-derived-macrophages
#11
Walther Haenseler, Federico Zambon, Heyne Lee, Jane Vowles, Federica Rinaldi, Galbha Duggal, Henry Houlden, Katrina Gwinn, Selina Wray, Kelvin C Luk, Richard Wade-Martins, William S James, Sally A Cowley
To examine the pathogenic role of α-synuclein (αS) in Parkinson's Disease, we have generated induced Pluripotent Stem Cell lines from early onset Parkinson's Disease patients with SNCA A53T and SNCA Triplication mutations, and in this study have differentiated them to PSC-macrophages (pMac), which recapitulate many features of their brain-resident cousins, microglia. We show that SNCA Triplication pMac, but not A53T pMac, have significantly increased intracellular αS versus controls and release significantly more αS to the medium...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28817274/notch-inhibitors-from-calotropis-gigantea-that-induce-neuronal-differentiation-of-neural-stem-cells
#12
Tatsuro Yoneyama, Midori A Arai, Ryuta Akamine, Kazune Koryudzu, Anna Tsuchiya, Samir K Sadhu, Firoj Ahmed, Motoyuki Itoh, Ryuichi Okamoto, Masami Ishibashi
Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease occur due to loss of the structure and function of neurons. For the potential treatment of neurodegenerative diseases, accelerators of neuronal differentiation of neural stem cells (NSCs) have been focused on and a cell-based assay system for measuring Notch signaling pathway activity was constructed. Using this assay system, eight compounds isolated from Calotropis gigantea were identified as inhibitors of the Notch signaling pathway...
August 17, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28760504/protection-against-rage-mediated-neuronal-cell-death-by-srage-secreting-human-mesenchymal-stem-cells-in-5xfad-transgenic-mouse-model
#13
Myeongjoo Son, Seyeon Oh, Hyunjin Park, Hyosang Ahn, Junwon Choi, Hyungho Kim, Hye Sun Lee, Sojung Lee, Hye-Jeong Park, Seung U Kim, Bonghee Lee, Kyunghee Byun
Alzheimer's disease (AD), which is the most commonly encountered neurodegenerative disease, causes synaptic dysfunction and neuronal loss due to various pathological processes that include tau abnormality and amyloid beta (Aβ) accumulation. Aβ stimulates the secretion and the synthesis of Receptor for Advanced Glycation End products (RAGE) ligand by activating microglial cells, and has been reported to cause neuronal cell death in amyloid beta1-42 treated rats and in mice with neurotoxin-induced Parkinson's disease...
July 28, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28748763/induced-pluripotent-stem-cell-technology-a-paradigm-shift-in-medical-science-for-drug-screening-and-disease-modeling
#14
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/28741230/new-therapeutic-strategies-for-lewy-body-dementias
#15
REVIEW
Latha Velayudhan, Dominic Ffytche, Clive Ballard, Dag Aarsland
This article reviews current treatment strategies and recent advances for the Lewy body dementias (LBDs). Current available symptom treatment strategies are based on monoaminergic, cholinergic and glutaminergic neurotransmitter systems. Relatively robust evidence exists for cholinesterase inhibitors for cognitive impairment in LBD and in Parkinson's disease for antidepressants, clozapine and recently pimavanserin for psychosis. interpidine (RVT 101) and nelotanserin are currently under investigation. Non-pharmacological interventions, such as cognitive stimulation, physical exercises and neuromodulation strategies, may be useful in Parkinson's disease but have not yet been tested in dementias...
September 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28731447/chromatin-bound-oxidized-%C3%AE-synuclein-causes-strand-breaks-in-neuronal-genomes-in-in-vitro-models-of-parkinson-s-disease
#16
Velmarini Vasquez, Joy Mitra, Pavana M Hegde, Arvind Pandey, Shiladitya Sengupta, Sankar Mitra, K S Rao, Muralidhar L Hegde
Alpha-synuclein (α-Syn) overexpression and misfolding/aggregation in degenerating dopaminergic neurons have long been implicated in Parkinson's disease (PD). The neurotoxicity of α-Syn is enhanced by iron (Fe) and other pro-oxidant metals, leading to generation of reactive oxygen species in PD brain. Although α-Syn is predominantly localized in presynaptic nerve terminals, a small fraction exists in neuronal nuclei. However, the functional and/or pathological role of nuclear α-Syn is unclear. Following up on our earlier report that α-Syn directly binds DNA in vitro, here we confirm the nuclear localization and chromatin association of α-Syn in neurons using proximity ligation and chromatin immunoprecipitation analysis...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28725655/cell-replacement-therapy-is-the-remedial-solution-for-treating-parkinson-s-disease
#17
REVIEW
Venkatesan Dhivya, Vellingiri Balachandar
The selective degeneration of dopaminergic (DA) neurons in Parkinson's disease (PD) has made an idol target for cell replacement therapies and other emerging surgical treatments. Certainly, by transplantation method, the therapeutic regimens such as human fetal ventral midbrain (hfVM) cells, human embryonic stem cells (hESCs), human neural stem/precursor/ progenitor cells (hNSCs/hNPCs), human mesenchymal stem cells (hMSCs), human induced neural stem cells (hiNSCs), and human induced pluripotent stem cells (hiPSCs) have been used into DA deficient striatum...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28724963/midnolin-is-a-novel-regulator-of-parkin-expression-and-is-associated-with-parkinson-s-disease
#18
Yutaro Obara, Toru Imai, Hidenori Sato, Yuji Takeda, Takeo Kato, Kuniaki Ishii
Midnolin (MIDN) was first discovered in embryonic stem cells, but its physiological and pathological roles are, to date, poorly understood. In the present study, we therefore examined the role of MIDN in detail. We found that in PC12 cells, a model of neuronal cells, MIDN localized primarily to the nucleus and intracellular membranes. Nerve growth factor promoted MIDN gene expression, which was attenuated by specific inhibitors of extracellular signal-regulated kinases 1/2 and 5. MIDN-deficient PC12 cells created using CRISPR/Cas9 technology displayed significantly impaired neurite outgrowth...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28696436/reduced-trpc6-mrna-levels-in-the-blood-cells-of-patients-with-alzheimer-s-disease-and-mild-cognitive-impairment
#19
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/28689993/mapt-genetic-variation-and-neuronal-maturity-alter-isoform-expression-affecting-axonal-transport-in-ipsc-derived-dopamine-neurons
#20
Joel E Beevers, Mang Ching Lai, Emma Collins, Heather D E Booth, Federico Zambon, Laura Parkkinen, Jane Vowles, Sally A Cowley, Richard Wade-Martins, Tara M Caffrey
The H1 haplotype of the microtubule-associated protein tau (MAPT) locus is genetically associated with neurodegenerative diseases, including Parkinson's disease (PD), and affects gene expression and splicing. However, the functional impact on neurons of such expression differences has yet to be fully elucidated. Here, we employ extended maturation phases during differentiation of induced pluripotent stem cells (iPSCs) into mature dopaminergic neuronal cultures to obtain cultures expressing all six adult tau protein isoforms...
August 8, 2017: Stem Cell Reports
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