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Parkinson disease and stem cell

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https://www.readbyqxmd.com/read/29339826/using-intracellular-markers-to-identify-a-novel-set-of-surface-markers-for-live-cell-purification-from-a-heterogeneous-hipsc-culture
#1
Elizabeth J Paik, Alison L O'Neil, Shi-Yan Ng, Chicheng Sun, Lee L Rubin
Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can provide sources for midbrain dopaminergic (mDA) neural progenitors (NPCs) for cell therapy to treat Parkinson's disease (PD) patients. However, the well-known line-to-cell line variability in the differentiation capacity of individual cell lines needs to be improved for the success of this therapy. To address this issue, we sought to identify mDA NPC specific cell surface markers for fluorescence activated cell sorting (FACS). Through RNA isolation after sorting for NPCs based on staining for cell-specific transcription factors followed by microarray, we identified two positive cell surface markers (CORIN and CD166) and one negative cell surface marker (CXCR4) for mDA NPC sorting...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29338785/benefits-of-vce-003-2-a-cannabigerol-quinone-derivative-against-inflammation-driven-neuronal-deterioration-in-experimental-parkinson-s-disease-possible-involvement-of-different-binding-sites-at-the-ppar%C3%AE-receptor
#2
Concepción García, María Gómez-Cañas, Sonia Burgaz, Belén Palomares, Yolanda Gómez-Gálvez, Cristina Palomo-Garo, Sara Campo, Joel Ferrer-Hernández, Carolina Pavicic, Carmen Navarrete, M Luz Bellido, Moisés García-Arencibia, M Ruth Pazos, Eduardo Muñoz, Javier Fernández-Ruiz
BACKGROUND: Neuroprotection with cannabinoids in Parkinson's disease (PD) has been afforded predominantly with antioxidant or anti-inflammatory cannabinoids. In the present study, we investigated the anti-inflammatory and neuroprotective properties of VCE-003.2, a quinone derivative of the non-psychotrophic phytocannabinoid cannabigerol (CBG), which may derive its activity at the peroxisome proliferator-activated receptor-γ (PPARγ). The compound is also an antioxidant. METHODS: We evaluated VCE-003...
January 16, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29338033/intermittent-low-dose-carbon-monoxide-exposure-enhances-survival-and-dopaminergic-differentiation-of-human-neural-stem-cells
#3
Nanna Dreyer-Andersen, Ana Sofia Almeida, Pia Jensen, Morad Kamand, Justyna Okarmus, Tine Rosenberg, Stig Düring Friis, Alberto Martínez Serrano, Morten Blaabjerg, Bjarne Winther Kristensen, Troels Skrydstrup, Jan Bert Gramsbergen, Helena L A Vieira, Morten Meyer
Exploratory studies using human fetal tissue have suggested that intrastriatal transplantation of dopaminergic neurons may become a future treatment for patients with Parkinson's disease. However, the use of human fetal tissue is compromised by ethical, regulatory and practical concerns. Human stem cells constitute an alternative source of cells for transplantation in Parkinson's disease, but efficient protocols for controlled dopaminergic differentiation need to be developed. Short-term, low-level carbon monoxide (CO) exposure has been shown to affect signaling in several tissues, resulting in both protection and generation of reactive oxygen species...
2018: PloS One
https://www.readbyqxmd.com/read/29334630/generation-of-an-integration-free-induced-pluripotent-stem-cell-line-csc-43j-from-a-patient-with-sporadic-parkinson-s-disease
#4
Ana Marote, Yuriy Pomeshchik, Stefano Goldwurm, Anna Collin, Nuno J Lamas, Luísa Pinto, António J Salgado, Laurent Roybon
An induced pluripotent stem cell (iPSC) line was generated from a 36-year-old patient with sporadic Parkinson's disease (PD). Skin fibroblasts were reprogrammed using the non-integrating Sendai virus technology to deliver OCT3/4, SOX2, c-MYC and KLF4 factors. The generated cell line (CSC-43) exhibits expression of common pluripotency markers, in vitro differentiation into three germ layers and normal karyotype. This iPSC line can be used to study the mechanisms underlying the development of PD.
January 4, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29334629/generation-of-a-human-induced-pluripotent-stem-cell-line-csc-42-from-a-patient-with-sporadic-form-of-parkinson-s-disease
#5
Ekaterina Savchenko, Ana Marote, Kaspar Russ, Anna Collin, Stefano Goldwurm, Laurent Roybon, Yuriy Pomeshchik
Skin fibroblasts were collected from a 44-year-old patient with sporadic case of Parkinson's disease (PD). The non-integrating Sendai virus vector encoding OCT3/4, SOX2, c-MYC and KLF4 was used to reprogram fibroblasts into induced pluripotent stem cells (iPSCs). Generated iPSCs had normal karyotypes, expressed common stem cell markers, and were capable of differentiating into all three germ layers. Generated line could be used for PD modeling to understand the mechanisms that influence the disorder.
January 4, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29331938/generation-of-a-human-induced-pluripotent-stem-cell-line-csc-40-from-a-parkinson-s-disease-patient-with-a-pink1-p-q456x-mutation
#6
Kaspar Russ, Ana Marote, Ekaterina Savchenko, Anna Collin, Stefano Goldwurm, Yuriy Pomeshchik, Laurent Roybon
Parkinson's disease (PD) is a neurodegenerative disease with unknown etiology. Here we show the generation of an induced pluripotent stem cell (iPSC) line, named CSC-40, from dermal fibroblasts obtained from a 59-year-old male patient with a homozygous p.Q456X mutation in the PTEN-induced putative kinase 1 (PINK/PARK6) gene and a confirmed diagnosis of PD, which could be used to model familial PD. A non-integrating Sendai virus-based delivery of the reprogramming factors OCT3/4, SOX2, c-MYC and KLF4 was employed...
January 4, 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29331684/reprogramming-neurodegeneration-in-the-big-data-era
#7
REVIEW
Lujia Zhou, Patrik Verstreken
Recent genome-wide association studies (GWAS) have identified numerous genetic risk variants for late-onset Alzheimer's disease (AD) and Parkinson's disease (PD). However, deciphering the functional consequences of GWAS data is challenging due to a lack of reliable model systems to study the genetic variants that are often of low penetrance and non-coding identities. Pluripotent stem cell (PSC) technologies offer unprecedented opportunities for molecular phenotyping of GWAS variants in human neurons and microglia...
January 10, 2018: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29327199/glycogen-synthase-kinase-3%C3%AE-regulates-equilibrium-between-neurogenesis-and-gliogenesis-in-rat-model-of-parkinson-s-disease-a-crosstalk-with-wnt-and-notch-signaling
#8
Sonu Singh, Akanksha Mishra, Sachi Bharti, Virendra Tiwari, Jitendra Singh, Parul, Shubha Shukla
Neurogenesis involves generation of functional newborn neurons from neural stem cells (NSCs). Insufficient formation or accelerated degeneration of newborn neurons may contribute to the severity of motor/nonmotor symptoms of Parkinson's disease (PD). However, the functional role of adult neurogenesis in PD is yet not explored and whether glycogen synthase kinase-3β (GSK-3β) affects multiple steps of adult neurogenesis in PD is still unknown. We investigated the possible underlying molecular mechanism of impaired adult neurogenesis associated with PD...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29321139/bmp-smad-pathway-promotes-neurogenesis-of-midbrain-dopaminergic-neurons-in-vivo-and-in-human-induced-pluripotent-and-neural-stem-cells
#9
V M Jovanovic, A Salti, H Tilleman, K Zega, M M Jukic, H Zou, R H Friedel, N Prakash, S Blaess, F Edenhofer, C Brodski
The embryonic formation of midbrain dopaminergic (mDA) neurons in vivo provides critical guidelines for the in vitro differentiation of mDA neurons from stem cells, currently being developed for Parkinson's disease cell replacement therapy. Bone morphogenetic protein (BMP)/SMAD inhibition is routinely used during early steps of stem cell differentiation protocols, including for the generation of mDA neurons. However, the function of the BMP/SMAD pathway for in vivo specification of mammalian mDA neurons is virtually unknown...
January 10, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29311330/gba1-deficiency-negatively-affects-physiological-%C3%AE-synuclein-tetramers-and-related-multimers
#10
Sangjune Kim, Seung Pil Yun, Saebom Lee, George Essien Umanah, Veera Venkata Ratnam Bandaru, Xiling Yin, Peter Rhee, Senthilkumar S Karuppagounder, Seung-Hwan Kwon, Hojae Lee, Xiaobo Mao, Donghoon Kim, Akhilesh Pandey, Gabsang Lee, Valina L Dawson, Ted M Dawson, Han Seok Ko
Accumulating evidence suggests that α-synuclein (α-syn) occurs physiologically as a helically folded tetramer that resists aggregation. However, the mechanisms underlying the regulation of formation of α-syn tetramers are still mostly unknown. Cellular membrane lipids are thought to play an important role in the regulation of α-syn tetramer formation. Since glucocerebrosidase 1 (GBA1) deficiency contributes to the aggregation of α-syn and leads to changes in neuronal glycosphingolipids (GSLs) including gangliosides, we hypothesized that GBA1 deficiency may affect the formation of α-syn tetramers...
January 8, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29311261/towards-stem-cell-based-therapies-for-parkinson-s-disease
#11
Malin Parmar
Treating neurodegenerative diseases with cell transplantation has been within reach since the first pioneering clinical trials in which dopamine neuron progenitors from the fetal brain were transplanted to individuals with Parkinson's disease. However, the use of fetal tissue is problematic in terms of low availability and high variability, and it is also associated with ethical concerns that vary between countries. For decades, the field has therefore investigated new scalable source of therapeutic cells from stem cells or via reprogramming...
January 8, 2018: Development
https://www.readbyqxmd.com/read/29309310/nuclear-translocation-of-dj-1-protects-adult-neuronal-stem-cells-in-an-mptp-mouse-model-of-parkinson-s-disease
#12
Yi Sun, Yupeng Wang, Xin Zhao, Xiaoping Pu
DJ-1, originally identified as an oncogene product, is involved in multiple processes, including cellular transformation, the oxidative stress response, and transcriptional regulation. We had previously found that DJ-1 was closely associated with the proliferation and differentiation of cultured neuronal stem cells. In this study, we further investigated the functions of DJ-1 to determine how adult neurogenesis was affected in the subgranular zones (SGZ), subventricular zone (SVZ), and olfactory bulb (OB), which are brain areas closely related to early nonmotor symptoms of Parkinson's disease, using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease...
January 5, 2018: Neuroreport
https://www.readbyqxmd.com/read/29234887/ips-cells-in-the-study-of-pd-molecular-pathogenesis
#13
REVIEW
Melanie M Cobb, Abinaya Ravisankar, Gaia Skibinski, Steven Finkbeiner
Parkinson's disease (PD) is the second most common neurodegenerative disease and its pathogenic mechanisms are poorly understood. The majority of PD cases are sporadic but a number of genes are associated with familial PD. Sporadic and familial PD have many molecular and cellular features in common, suggesting some shared pathogenic mechanisms. Induced pluripotent stem cells (iPSCs) have been derived from patients harboring a range of different mutations of PD-associated genes. PD patient-derived iPSCs have been differentiated into relevant cell types, in particular dopaminergic neurons and used as a model to study PD...
December 12, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29234401/trans-cinnamaldehyde-inhibits-microglial-activation-and-improves-neuronal-survival-against-neuroinflammation-in-bv2-microglial-cells-with-lipopolysaccharide-stimulation
#14
Yan Fu, Pin Yang, Yang Zhao, Liqing Zhang, Zhangang Zhang, Xianwen Dong, Zhongping Wu, Ying Xu, Yongjun Chen
Background: Microglial activation contributes to neuroinflammation and neuronal damage in neurodegenerative disorders including Alzheimer's and Parkinson's diseases. It has been suggested that neurodegenerative disorders may be improved if neuroinflammation can be controlled. trans-cinnamaldehyde (TCA) isolated from the stem bark of Cinnamomum cassia possesses potent anti-inflammatory capability; we thus tested whether TCA presents neuroprotective effects on improving neuronal survival by inhibiting neuroinflammatory responses in BV2 microglial cells...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29227287/creating-a-graft-friendly-environment-for-stem-cells-in-diseased-brains
#15
Robert Yl Tsai
Most of the adult CNS lacks regenerative activity in terms of both neuron birth and neurite outgrowth. While this regeneration-unfriendly environment of the adult CNS may preserve the existing neuronal circuitry that takes years to develop in higher organisms, it also poses a major obstacle for CNS repair later in life. In this issue of the JCI, Song et al. report on their development of a strategy that uses region-specific and molecularly engineered astrocytes to turn an unfavorable brain environment into a favorable one for engrafted neural stem/progenitor cells (NSC/NPCs)...
December 11, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29217686/synaptic-regulator-%C3%AE-synuclein-in-dopaminergic-fibers-is-essentially-required-for-the-maintenance-of-subependymal-neural-stem-cells
#16
Ana Perez-Villalba, Mª Salomé Sirerol-Piquer, Germán Belenguer, Raúl Soriano-Cantón, Ana Belén Muñoz-Manchado, Javier Villadiego, Diana Alarcón-Arís, Federico N Soria, Benjamin Dehay, Erwan Bezard, Miquel Vila, Analía Bortolozzi, Juan José Toledo-Aral, Francisco Pérez-Sánchez, Isabel Fariñas
Synaptic protein α-synuclein (α-SYN) modulates neurotransmission in a complex and poorly understood manner and aggregates in the cytoplasm of degenerating neurons in Parkinson's disease. Here, we report that α-SYN present in dopaminergic nigral afferents is essential for the normal cycling and maintenance of neural stem cells (NSCs) in the brain subependymal zone of adult male and female mice. We also show that premature senescence of adult NSCs into non-neurogenic astrocytes in mice lacking α-SYN resembles the effects of dopaminergic fiber degeneration resulting from chronic exposure to MPTP or intranigral inoculation of aggregated toxic α-SYN...
December 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29212273/repositioning-cep-1347-a-chemical-agent-originally-developed-for-the-treatment-of-parkinson-s-disease-as-an-anti-cancer-stem-cell-drug
#17
Masashi Okada, Hiroyuki Takeda, Hirotsugu Sakaki, Kenta Kuramoto, Shuhei Suzuki, Tomomi Sanomachi, Keita Togashi, Shizuka Seino, Chifumi Kitanaka
CEP-1347 is a mixed lineage kinase inhibitor tested in a large-scale phase 2/3 clinical trial in early Parkinson's disease, in which its safety and tolerability, but nevertheless not efficacy, was demonstrated. Here we identify by drug repositioning CEP-1347 as a potential anti-cancer stem cell drug. In vitro, CEP-1347 efficiently induced differentiation and inhibited the self-renewal and tumor-initiating capacities of human cancer stem cells from glioblastoma as well as from pancreatic and ovarian cancers at clinically-relevant concentrations, without impairing the viability of normal fibroblasts and neural stem cells...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207913/generation-of-dopamine-secreting-cells-from-human-adipose-tissue-derived-stem-cells-in-vitro
#18
Mohammad Hasan Soheilifar, Arash Javeri, Hossein Amini, Masoumeh Fakhr Taha
Several studies have demonstrated the differentiation of human adipose tissue-derived stem cells (hADSCs) to neuronal and glial phenotypes, but directing the fate of these cells toward dopaminergic neurons has not been frequently reported. The aim of the present study was to investigate dopaminergic specification of hADSCs in vitro. ADSCs were isolated from subcutaneous abdominal adipose tissue and were characterized. For dopaminergic differentiation, a cocktail of sonic hedgehog, fibroblast growth factor 8, basic fibroblast growth factor and brain-derived neurotrophic factor were used under a low serum condition...
December 5, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/29199243/daphnane-and-phorbol-diterpenes-anti-neuroinflammatory-compounds-with-nurr1-activation-from-the-roots-and-stems-of-daphne-genkwa
#19
Baek-Soo Han, Nguyen Van Minh, Ha-Young Choi, Jung-Su Byun, Won-Gon Kim
The methanol extract of the roots and stems of Daphne genkwa and its constituents yuanhuacin (1) and genkwanine N were previously reported to have Nurr1 activating effects and neuroprotective effects in an animal model of Parkinson's disease (PD). In this study, four more daphnane-type diterpenes (acutilonine F (2), wikstroemia factor M1 (3), yuanhuadine (5), and yuanhuatine (6)) and two phorbol-type diterpenes (prostratin Q (4) and 12-O-n-deca-2,4,6-trienoyl-phorbol-(13)-acetate (7)) were isolated as Nurr1 activating compounds from the D...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29188600/killing-two-birds-with-one-stone-the-multifunctional-roles-of-mesenchymal-stem-cells-in-the-treatment-of-neurodegenerative-and-muscle-diseases
#20
REVIEW
Na Kyung Lee, Duk L Na, Jong Wook Chang
Neurodegenerative and muscle diseases bear both complex and multifactorial pathologies. An efficacious and robust therapeutic option to treat these diseases is yet to be elucidated. At such a time, mesenchymal stem cells have drawn significant attention due to their immunomodulatory and regenerative properties. Accumulating evidence has proposed the capability of MSCs to serve multiple roles in a broad spectrum of diseases by secretion of trophic or paracrine factors. In the present review, we will look into the recent literature and discuss the therapeutic functions of MSCs and their potential to treat various neurodegenerative (Alzheimer's, Parkinson's, and Huntington's disease) and muscle (Duchenne muscular dystrophy, myopathy, and multiple sclerosis) diseases...
November 30, 2017: Histology and Histopathology
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