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Parkinson disease and stem cell

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https://www.readbyqxmd.com/read/28438892/brain-metabolism-in-health-aging-and%C3%A2-neurodegeneration
#1
REVIEW
Simonetta Camandola, Mark P Mattson
Brain cells normally respond adaptively to bioenergetic challenges resulting from ongoing activity in neuronal circuits, and from environmental energetic stressors such as food deprivation and physical exertion. At the cellular level, such adaptive responses include the "strengthening" of existing synapses, the formation of new synapses, and the production of new neurons from stem cells. At the molecular level, bioenergetic challenges result in the activation of transcription factors that induce the expression of proteins that bolster the resistance of neurons to the kinds of metabolic, oxidative, excitotoxic, and proteotoxic stresses involved in the pathogenesis of brain disorders including stroke, and Alzheimer's and Parkinson's diseases...
April 24, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28437187/synergy-between-choroid-plexus-epithelial-cells-conditioned-medium-and-knockout-serum-replacement-converts-human-adipose-derived-stem-cells-to-dopamine-secreting-neurons
#2
Mahdi Eskandarian Boroujeni, Mossa Gardaneh, Mehrnoosh Hasan Shahriari, Abbas Aliaghaei, Sanaz Hasani
Human adipose-derived stem cells (hADSCs) have great capacity to differentiate into mesodermal origins as well as non-mesodermal lineages including neural cells. This valuable feature paves the way for the therapeutic application of hADSCs for neurodegenerative maladies such as Parkinson's disease (PD). We tested the capacity of Choroid Plexus epithelial cells-conditioned medium (CPEC-CM) alone or cocktailed with knock-out serum (KS) to induce dopaminergic differentiation of hADSCs. To this end, hADSCs from lipoaspirate were phenotypically characterized and shown to maintain mesodermal multipotency so selected media easily differentiated them into osteoblasts, chondrocytes and adipocytes...
March 2, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28431219/genetic-analysis-of-%C3%AE-synuclein-3-untranslated-region-and-its-corresponding-micrornas-in-relation-to-parkinson-s-compared-to-dementia-with-lewy-bodies
#3
Lidia Tagliafierro, Omolara-Chinue Glenn, Madison E Zamora, Thomas G Beach, Randy L Woltjer, Michael W Lutz, Ornit Chiba-Falek
INTRODUCTION: The α-synuclein (SNCA) gene has been implicated in the etiology of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). METHODS: A computational analysis of SNCA 3' untranslated region to identify potential microRNA (miRNA) binding sites and quantitative real-time PCR to determine their expression in isogenic induced pluripotent stem cell-derived dopaminergic and cholinergic neurons as a model of PD and DLB, respectively, were performed. In addition, we performed a deep sequencing analysis of the SNCA 3' untranslated region of autopsy-confirmed cases of PD, DLB, and normal controls, followed by genetic association analysis of the identified variants...
April 18, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28430167/induced-pluripotent-stem-cell-modeling-of-gaucher-s-disease-what-have-we-learned
#4
REVIEW
Dino Matias Santos, Gustavo Tiscornia
Gaucher's disease (GD) is the most frequently inherited lysosomal storage disease, presenting both visceral and neurologic symptoms. Mutations in acid β-glucocerebrosidase disrupt the sphingolipid catabolic pathway promoting glucosylceramide (GlcCer) accumulation in lysosomes. Current treatment options are enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). However, neither of these approaches is effective in treating the neurological aspect of the disease. The use of small pharmacological compounds that act as molecular chaperones is a promising approach that is still experimental...
April 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28423196/melatonin-enhances-neural-stem-cell-differentiation-and-engraftment-by-increasing-mitochondrial-function
#5
Miguel Mendivil-Perez, Viviana Soto-Mercado, Ana Guerra-Librero, Beatriz I Fernandez-Gil, Javier Florido, Ying-Qiang Shen, Miguel A Tejada, Vivian Capilla-Gonzalez, Iryna Rusanova, José M Garcia-Verdugo, Darío Acuña-Castroviejo, Luis Carlos López, Carlos Velez-Pardo, Marlene Jimenez-Del-Rio, José M Ferrer, Germaine Escames
Neural stem cells (NSCs) are regarded as a promising therapeutic approach to protecting and restoring damaged neurons in neurodegenerative diseases (NDs) such as Parkinson's disease and Alzheimer's disease (PD and AD, respectively). However, new research suggests that NSC differentiation is required to make this strategy effective. Several studies have demonstrated that melatonin increases mature neuronal markers, which reflects NSC differentiation into neurons. Nevertheless, the possible involvement of mitochondria in the effects of melatonin during NSC differentiation has not yet been fully established...
April 19, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28416701/defective-synaptic-connectivity-and-axonal-neuropathology-in-a-human-ipsc-based-model-of-familial-parkinson-s-disease
#6
Georgia Kouroupi, Era Taoufik, Ioannis S Vlachos, Konstantinos Tsioras, Nasia Antoniou, Florentia Papastefanaki, Dafni Chroni-Tzartou, Wolfgang Wrasidlo, Delphine Bohl, Dimitris Stellas, Panagiotis K Politis, Kostas Vekrellis, Dimitra Papadimitriou, Leonidas Stefanis, Piotr Bregestovski, Artemis G Hatzigeorgiou, Eliezer Masliah, Rebecca Matsas
α-Synuclein (αSyn) is the major gene linked to sporadic Parkinson's disease (PD), whereas the G209A (p.A53T) αSyn mutation causes a familial form of PD characterized by early onset and a generally severe phenotype, including nonmotor manifestations. Here we generated de novo induced pluripotent stem cells (iPSCs) from patients harboring the p.A53T mutation and developed a robust model that captures PD pathogenic processes under basal conditions. iPSC-derived mutant neurons displayed novel disease-relevant phenotypes, including protein aggregation, compromised neuritic outgrowth, and contorted or fragmented axons with swollen varicosities containing αSyn and Tau...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28416282/derivation-of-human-midbrain-specific-organoids-from-neuroepithelial-stem%C3%A2-cells
#7
Anna S Monzel, Lisa M Smits, Kathrin Hemmer, Siham Hachi, Edinson Lucumi Moreno, Thea van Wuellen, Javier Jarazo, Jonas Walter, Inga Brüggemann, Ibrahim Boussaad, Emanuel Berger, Ronan M T Fleming, Silvia Bolognin, Jens C Schwamborn
Research on human brain development and neurological diseases is limited by the lack of advanced experimental in vitro models that truly recapitulate the complexity of the human brain. Here, we describe a robust human brain organoid system that is highly specific to the midbrain derived from regionally patterned neuroepithelial stem cells. These human midbrain organoids contain spatially organized groups of dopaminergic neurons, which make them an attractive model for the study of Parkinson's disease. Midbrain organoids are characterized in detail for neuronal, astroglial, and oligodendrocyte differentiation...
March 31, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28413004/derivation-of-human-induced-pluripotent-stem-cell-ipsc-line-from-a-79year-old-sporadic-male-parkinson-s-disease-patient
#8
Shaokun Zhang, Lidi Liu, Yang Hu, Zhenshan Lv, Qiao Li, Weiquan Gong, Hui Sha, Hong Wu
Peripheral blood was collected from a clinically diagnosed 79-year old male sporadic Parkinson's disease patient. 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 can be used to study the mechanism of sporadic Parkinson's disease and to test new drugs...
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28413000/derivation-of-mouse-embryonic-stem-cell-lines-from-tyrosine-hydroxylase-reporter-mice-crossed-with-a-human-snca-transgenic-mouse-model-of-parkinson-s-disease
#9
Margarita Chumarina, Carla Azevedo, Julie Bigarreau, Clémentine Vignon, Kwang-Soo Kim, Jia-Yi Li, Laurent Roybon
Mouse embryonic stem cell (mESC) lines were derived by crossing heterozygous transgenic (tg) mice expressing green fluorescent protein (GFP) under the control of the rat tyrosine hydroxylase (TH) promoter, with homozygous alpha-synuclein (aSYN) mice expressing human mutant SNCA(A53T) under the control of the mouse Prion promoter (MoPrP), or wildtype (WT) mice. The expression of GFP and human aSYN was validated by immunocytochemistry in midbrain neuron cultures upon differentiation of mESC lines using stromal cell-derived inducing activity...
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28407791/accelerated-differentiation-of-human-induced-pluripotent-stem-cells-to-blood-brain-barrier-endothelial-cells
#10
Emma K Hollmann, Amanda K Bailey, Archit V Potharazu, M Diana Neely, Aaron B Bowman, Ethan S Lippmann
BACKGROUND: Due to their ability to limitlessly proliferate and specialize into almost any cell type, human induced pluripotent stem cells (iPSCs) offer an unprecedented opportunity to generate human brain microvascular endothelial cells (BMECs), which compose the blood-brain barrier (BBB), for research purposes. Unfortunately, the time, expense, and expertise required to differentiate iPSCs to purified BMECs precludes their widespread use. Here, we report the use of a defined medium that accelerates the differentiation of iPSCs to BMECs while achieving comparable performance to BMECs produced by established methods...
April 13, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/28396625/cd133-positive-membrane-particles-in-cerebrospinal-fluid-of-patients-with-inflammatory-and-degenerative-neurological-diseases
#11
Tobias Bobinger, Lisa May, Hannes Lücking, Stephan P Kloska, Petra Burkardt, Philipp Spitzer, Juan M Maler, Denis Corbeil, Hagen B Huttner
Background: Analysis of cerebrospinal fluid (CSF) is a frequently used diagnostic tool in a variety of neurological diseases. Recent studies suggested that investigating membrane particles enriched with the stem cell marker CD133 may offer new avenues for studying neurological disease. In this study, we evaluated the amount of membrane particle-associated CD133 in human CSF in neuroinflammatory and degenerative diseases. Methods: We compared the amount of membrane particle-associated CD133 in CSF samples collected from 45 patients with normal pressure hydrocephalus, parkinsonism, dementia, and cognitive impairment, chronic inflammatory diseases and 10 healthy adult individuals as controls...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28395805/generation-of-a-human-induced-pluripotent-stem-cell-ipsc-line-carrying-the-parkinson-s-disease-linked-lrrk2-variant-s1647t
#12
Dongrui Ma, Shin Hui Ng, Li Zeng, Yi Zhao, Eng King Tan
Peripheral blood mononuclear cells (PBMCs) were collected from a clinically diagnosed 64-year old male Parkinson's disease (PD) patient with S1647T variant in the LRRK2 gene. The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus reprogramming system. The transgene-free iPSC showed pluripotency confirmed by immunofluorescent staining for pluripotency markers and differentiated into the 3 germ layers in vivo. The iPSC line also showed normal karyotype. This cellular model will be useful for further function studies and therapeutic screening...
January 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28395804/development-of-a-human-induced-pluripotent-stem-cell-ipsc-line-from-a-parkinson-s-disease-patient-carrying-the-n551k-variant-in-lrrk2-gene
#13
Dongrui Ma, Ebonne Yulin Ng, Li Zeng, Christina Ying Yan Lim, Yi Zhao, Eng King Tan
Peripheral blood mononuclear cells (PBMCs) were collected from a clinically diagnosed 64-year old male Parkinson's disease (PD) patient with N551K variant in the LRRK2 gene. The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus reprogramming system. The transgene-free iPSC showed pluripotency confirmed by immunofluorescent staining for pluripotency markers and differentiated into the 3 germ layers in vivo. The iPSC line also showed normal karyotype. This cellular model can complement in vivo PD models for pathophysiological studies and drug screening...
January 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28395803/derivation-of-human-induced-pluripotent-stem-cell-ipsc-line-with-lrrk2-gene-r1398h-variant-in-parkinson-s-disease
#14
Dongrui Ma, Murni Tio, Shin Hui Ng, Li Zeng, Christina Ying Yan Lim, Yi Zhao, Eng King Tan
Peripheral blood mononuclear cells (PBMCs) were collected from a clinically diagnosed 72-year old female Parkinson's disease (PD) patient with R1398H variant in the LRRK2 gene. The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus reprogramming system. The transgene-free iPSC showed pluripotency confirmed by immunofluorescent staining for pluripotency markers and differentiated into the 3 germ layers in vivo. The iPSC line also showed normal karyotype. This cellular model provides a good platform for studying the mechanism of PD, and also for drug testing and gene therapy studies...
January 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28395802/reprogramming-of-a-human-induced-pluripotent-stem-cell-ipsc-line-from-a-parkinson-s-disease-patient-with-a-r1628p-variant-in-the-lrrk2-gene
#15
Dongrui Ma, Wei Zhou, Ebonne Yulin Ng, Li Zeng, Yi Zhao, Eng King Tan
Peripheral blood mononuclear cells (PBMCs) were collected from a clinically diagnosed 59-year old male Parkinson's disease (PD) patient with R1628P variant in the LRRK2 gene. The PMBCs were reprogrammed with the human OSKM transcription factors using the Sendai-virus reprogramming system. The transgene-free iPSC showed pluripotency confirmed by immunofluorescent staining for pluripotency markers and differentiated into the 3 germ layers in vivo. The iPSC line also showed normal karyotype. This cellular model will provide a good resource for further pathophysiological studies of PD...
January 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28379402/slp-2-interacts-with-parkin-in-mitochondria-and-prevents-mitochondrial-dysfunction-in-parkin-deficient-human-ipsc-derived-neurons-and-drosophila
#16
Alessandra Zanon, Sreehari Kalvakuri, Aleksandar Rakovic, Luisa Foco, Marianna Guida, Christine Schwienbacher, Alice Serafin, Franziska Rudolph, Michaela Trilck, Anne Grünewald, Nancy Stanslowsky, Florian Wegner, Valentina Giorgio, Alexandros A Lavdas, Rolf Bodmer, Peter P Pramstaller, Christine Klein, Andrew A Hicks, Irene Pichler, Philip Seibler
Mutations in the Parkin gene (PARK2) have been linked to a recessive form of Parkinson's disease (PD) characterized by the loss of dopaminergic neurons in the substantia nigra. Deficiencies of mitochondrial respiratory chain complex I activity have been observed in the substantia nigra of PD patients, and loss of Parkin results in the reduction of complex I activity shown in various cell and animal models. Using co-immunoprecipitation and proximity ligation assays on endogenous proteins, we demonstrate that Parkin interacts with mitochondrial Stomatin-like protein 2 (SLP-2), which also binds the mitochondrial lipid cardiolipin and functions in the assembly of respiratory chain proteins...
April 3, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28370445/media-hype-patient-and-scientific-perspectives-on-misleading-medical-news
#17
Israel Robledo, Joseph Jankovic
In this age of digital technology, Internet, and social media we are increasingly subjected to an information and disinformation overload. This includes not only political and economic information but also medical news, which is often presented as a "new discovery", "miracle cure" or some other press hyperbole. In this viewpoint article we present patient and scientific perspectives some recent episodes of medical hype related to Parkinson's disease research, including proposed therapies such as nilotinib, marijuana, stem cells and other controversial therapies that have attracted the mainstream and social media...
April 3, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28369799/effect-of-dental-pulp-stem-cells-in-mptp-induced-old-aged-mice-model
#18
Nareshwaran Gnanasegaran, Vijayendran Govindasamy, Christopher Simon, Quan Fu Gan, Vui King Vincent-Chong, Vasudevan Mani, Kesavanarayanan Krishnan Selvarajan, Vellayan Subramaniam, Sabri Musa, Noor Hayaty Abu Kasim
BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic (DA-ergic) neurons in the substantia nigra (SN) and represented as a huge threat to the geriatric population. Cell replacement therapies (CRTs) have been proposed as a promising strategy to slow down or replace neuronal loss. Among the widely available cell sources, dental pulp stem cells (DPSCs) portray as an attractive source primarily due to their neural crest origin, ease of tissue procurement and less ethical hurdles...
March 30, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28356028/the-application-of-nanomaterials-in-stem-cell-therapy-for-some-neurological-diseases
#19
Guilong Zhang, Ahsan Ali Khan, Hao Wu, Lukui Chen, Yuchun Gu, Ning Gu
Stem cell therapy provides great promising therapeutic benefits for various neurological disorders. Cell transplantation has emerged as cell replacement application for nerve damage. Recently, nanomaterials obtain wide development in various industrial and medical fields, and nanoparticles have been applied to neuro-medical field for tracking and treating nervous system diseases. Combining stem cell with nanotechnology has raised more and more attentions; and it has demonstrated that it has huge effects on clinical diagnosis and therapeutics in multiple central nervous system diseases, meanwhile, improving prognosis...
March 28, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28348207/nurr1-rxr%C3%AE-heterodimer-activation-as-monotherapy-for-parkinson-s-disease
#20
Athanasios D Spathis, Xenophon Asvos, Despina Ziavra, Theodoros Karampelas, Stavros Topouzis, Zoe Cournia, Xiaobing Qing, Pavlos Alexakos, Lisa M Smits, Christina Dalla, Hardy J Rideout, Jens Christian Schwamborn, Constantin Tamvakopoulos, Demosthenes Fokas, Demetrios K Vassilatis
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra and the gradual depletion of dopamine (DA). Current treatments replenish the DA deficit and improve symptoms but induce dyskinesias over time, and neuroprotective therapies are nonexistent. Here we report that Nuclear receptor-related 1 (Nurr1):Retinoid X receptor α (RXRα) activation has a double therapeutic potential for PD, offering both neuroprotective and symptomatic improvement...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
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