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dopaminergic stem cells

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https://www.readbyqxmd.com/read/29650976/wnt-signal-activation-induces-midbrain-specification-through-direct-binding-of-the-beta-catenin-tcf4-complex-to-the-en1-promoter-in-human-pluripotent-stem-cells
#1
Ji Young Kim, Jae Souk Lee, Hyun Sub Hwang, Dongjin R Lee, Chul-Yong Park, Sung Jun Jung, Young Rang You, Dae-Sung Kim, Dong-Wook Kim
The canonical Wnt signal pathway plays a pivotal role in anteroposterior patterning and midbrain specification during early neurogenesis. Activating Wnt signal has been a strategy for differentiating human pluripotent stem cells (PSCs) into midbrain dopaminergic (DA) neurons; however, the underlying molecular mechanism(s) of how the Wnt signal drives posterior fate remained unclear. In this study, we found that activating the canonical Wnt signal significantly upregulated the expression of EN1, a midbrain-specific marker, in a fibroblast growth factor signal-dependent manner in human PSC-derived neural precursor cells (NPCs)...
April 13, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29604226/stem-cell-modeling-of-mitochondrial-parkinsonism-reveals-key-functions-of-opa1
#2
Mindaugas Jonikas, Martin Madill, Alexandre Mathy, Theresa Zekoll, Christos E Zois, Simon Wigfield, Marzena Kurzawa-Akanbi, Cathy Browne, David Sims, Patrick F Chinnery, Sally A Cowley, George K Tofaris
OBJECTIVE: Defective mitochondrial function due to OPA1 mutations causes primarily optic atrophy and less commonly neurodegenerative syndromes. The pathomechanism by which OPA1 mutations trigger diffuse loss of neurons in some but not all patients is unknown. Here we used a tractable iPSC-based model to capture the biology of OPA1 haploinsufficiency in cases presenting with classic eye disease versus syndromic parkinsonism. METHODS: iPSC were generated from two patients with OPA1 haploinsufficiency and two controls and differentiated into dopaminergic neurons...
March 31, 2018: Annals of Neurology
https://www.readbyqxmd.com/read/29577367/bioluminescence-driven-optogenetic-activation-of-transplanted-neural-precursor-cells-improves-motor-deficits-in-a-parkinson-s-disease-mouse-model
#3
Jessica R Zenchak, Brandon Palmateer, Nicolai Dorka, Tariq M Brown, Lina-Marie Wagner, William E Medendorp, Eric D Petersen, Mansi Prakash, Ute Hochgeschwender
The need to develop efficient therapies for neurodegenerative diseases is urgent, especially given the increasing percentages of the population living longer, with increasing chances of being afflicted with conditions like Parkinson's disease (PD). A promising curative approach toward PD and other neurodegenerative diseases is the transplantation of stem cells to halt and potentially reverse neuronal degeneration. However, stem cell therapy does not consistently lead to improvement for patients. Using remote stimulation to optogenetically activate transplanted cells, we attempted to improve behavioral outcomes of stem cell transplantation...
March 25, 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29575325/neural-stem-cell-grafts-promote-astroglia-driven-neurorestoration-in-the-aged-parkinsonian-brain-via-wnt-%C3%AE-catenin-signalling
#4
Francesca L'Episcopo, Cataldo Tirolo, Luca Peruzzotti-Jametti, Maria F Serapide, Nunzio Testa, Salvatore Caniglia, Beatrice Balzarotti, Stefano Pluchino, Bianca Marchetti
During aging - one the most potent risk factors for Parkinson's disease (PD) - both astrocytes and microglia undergo functional changes that ultimately hamper homoeostasis, defence and repair of substantia nigra pars compacta (SNpc) midbrain dopaminergic (mDA) neurons. We tested the possibility of rejuvenating the host microenvironment and boosting SNpc DA neuronal plasticity via the unilateral transplantation of syngeneic neural stem/progenitor cells (NSCs) in the SNpc of aged mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced experimental PD...
March 25, 2018: Stem Cells
https://www.readbyqxmd.com/read/29564810/kir6-2-deficiency-promotes-mesencephalic-neural-precursor-cell-differentiation-via-regulating-mir-133b-gdnf-in-a-parkinson-s-disease-mouse-model
#5
Yan Zhou, Jialei Zhu, Yang Lv, Chenghuan Song, Jianhua Ding, Ming Xiao, Ming Lu, Gang Hu
The loss of dopaminergic (DA) neurons in the substantia nigra (SN) is a major feature in the pathology of Parkinson's disease (PD). Using neural stem or progenitor cells (NSC/NPCs), the prospect of replacing the missing or damaged DA neurons is very attractive for PD therapy. However, little is known about the endogenous mechanisms and molecular pathways regulating the NSC/NPC proliferation and differentiation in the development of PD. Herein, using Kir6.2 knockout (Kir6.2-/- ) mice, we observed that genetic deficiency of Kir6...
March 21, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29534967/mitochondrial-dysfunction-in-dopaminergic-neurons-differentiated-from-exfoliated-deciduous-tooth-derived-pulp-stem-cells-of-a-child-with-rett-syndrome
#6
Saki Hirofuji, Yuta Hirofuji, Hiroki Kato, Keiji Masuda, Haruyoshi Yamaza, Hiroshi Sato, Fumiko Takayama, Michiko Torio, Yasunari Sakai, Shouichi Ohga, Tomoaki Taguchi, Kazuaki Nonaka
Rett syndrome is an X-linked neurodevelopmental disorder associated with psychomotor impairments, autonomic dysfunctions and autism. Patients with Rett syndrome have loss-of-function mutations in MECP2, the gene encoding methyl-CpG-binding protein 2 (MeCP2). Abnormal biogenic amine signaling and mitochondrial function have been found in patients with Rett syndrome; however, few studies have analyzed the association between these factors. This study investigated the functional relationships between mitochondria and the neuronal differentiation of the MeCP2-deficient stem cells from the exfoliated deciduous teeth of a child with Rett syndrome...
March 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29531524/ropinirole-and-pramipexole-promote-structural-plasticity-in-human-ipsc-derived-dopaminergic-neurons-via-bdnf-and-mtor-signaling
#7
Ginetta Collo, Laura Cavalleri, Federica Bono, Cristina Mora, Stefania Fedele, Roberto William Invernizzi, Massimo Gennarelli, Giovanna Piovani, Tilo Kunath, Mark J Millan, Emilio Merlo Pich, PierFranco Spano
The antiparkinsonian ropinirole and pramipexole are D3 receptor- (D3R-) preferring dopaminergic (DA) agonists used as adjunctive therapeutics for the treatment resistant depression (TRD). While the exact antidepressant mechanism of action remains uncertain, a role for D3R in the restoration of impaired neuroplasticity occurring in TRD has been proposed. Since D3R agonists are highly expressed on DA neurons in humans, we studied the effect of ropinirole and pramipexole on structural plasticity using a translational model of human-inducible pluripotent stem cells (hiPSCs)...
2018: Neural Plasticity
https://www.readbyqxmd.com/read/29512105/hpsc-derived-midbrain-dopaminergic-neurons-generated-in-a-scalable-3-d-biomaterial
#8
Maroof M Adil, David V Schaffer
Human pluripotent stem cell (hPSC)-derived midbrain dopaminergic (mDA) neurons may facilitate the development of therapies for Parkinson's disease via disease modeling, drug screening, and cell replacement therapy. However, large numbers of cells are typically needed for these applications, and 2-D culture-based approaches typically used for mDA differentiation are difficult to scale up and require a long time for mDA maturation. Here we present a protocol to rapidly generate functional mDA neurons in a fully defined, scalable, thermoresponsive 3-D biomaterial...
February 28, 2018: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/29511358/neuronal-subtype-generation-during-postnatal-olfactory-bulb-neurogenesis
#9
Alexandra Angelova, Marie-Catherine Tiveron, Harold Cremer, Christophe Beclin
In the perinatal and adult forebrain, regionalized neural stem cells lining the ventricular walls produce different types of olfactory bulb interneurons. Although these postnatal stem cells are lineage related to their embryonic counterparts that produce, for example, cortical, septal, and striatal neurons, their output at the level of neuronal phenotype changes dramatically. Tiveron et al. investigated the molecular determinants underlying stem cell regionalization and the gene expression changes inducing the shift from embryonic to adult neuron production...
2018: Journal of Experimental Neuroscience
https://www.readbyqxmd.com/read/29498713/effects-of-passage-number-and-differentiation-protocol-on-the-generation-of-dopaminergic-neurons-from-rat-bone-marrow-derived-mesenchymal-stem-cells
#10
Gabrielle Shall, Megan Menosky, Sarah Decker, Priya Nethala, Ryan Welchko, Xavier Leveque, Ming Lu, Michael Sandstrom, Ute Hochgeschwender, Julien Rossignol, Gary Dunbar
Multiple studies have demonstrated the ability of mesenchymal stem cells (MSCs) to differentiate into dopamine-producing cells, in vitro and in vivo, indicating their potential to be used in the treatment of Parkinson's disease (PD). However, there are discrepancies among studies regarding the optimal time (i.e., passage number) and method for dopaminergic induction, in vitro. In the current study, we compared the ability of early (P4) and later (P40) passaged bone marrow-derived MSCs to differentiate into dopaminergic neurons using two growth-factor-based approaches...
March 2, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29483868/microglia-polarization-gene-environment-interactions-and-wnt-%C3%AE-catenin-signaling-emerging-roles-of-glia-neuron-and-glia-stem-neuroprogenitor-crosstalk-for-dopaminergic-neurorestoration-in-aged-parkinsonian-brain
#11
REVIEW
Francesca L'Episcopo, Cataldo Tirolo, Maria F Serapide, Salvatore Caniglia, Nunzio Testa, Loredana Leggio, Silvia Vivarelli, Nunzio Iraci, Stefano Pluchino, Bianca Marchetti
Neuroinflammatory processes are recognized key contributory factors in Parkinson's disease (PD) physiopathology. While the causes responsible for the progressive loss of midbrain dopaminergic (mDA) neuronal cell bodies in the subtantia nigra pars compacta are poorly understood, aging, genetics, environmental toxicity, and particularly inflammation, represent prominent etiological factors in PD development. Especially, reactive astrocytes, microglial cells, and infiltrating monocyte-derived macrophages play dual beneficial/harmful effects, via a panel of pro- or anti-inflammatory cytokines, chemokines, neurotrophic and neurogenic transcription factors...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29471019/hsp90-co-chaperone-p23-contributes-to-dopaminergic-mitochondrial-stress-via-stabilization-of-phd2-implications-for-parkinson-s-disease
#12
Anand Rane, Subramanian Rajagopalan, Manuj Ahuja, Bobby Thomas, Shankar J Chinta, Julie K Andersen
The heat shock factor 90 (hsp90) complex has long been associated with neuropathological phenotypes linked to Parkinson's disease (PD) and its inhibition is neuroprotective in disease models. Hsp90 is conventionally believed to act by suppressing induction of hsp70. Here, we report a novel hsp70-independent mechanism by which Hsp90 may also contribute to PD-associated neuropathology. We previously reported that inhibition of the enzyme prolyl hydroxylase domain 2 (PHD2) in conjunction with increases in hypoxia-inducible factor 1 alpha (HIF1α) results in protection of vulnerable dopaminergic substantia nigra pars compacta (DAergic SNpc) neurons in in vitro and in vivo models of PD...
February 19, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29468158/central-and-peripheral-nervous-system-progenitors-derived-from-human-pluripotent-stem-cells-reveal-a-unique-temporal-and-cell-type-specific-expression-of-pmcas
#13
Muwan Chen, Sofie H Laursen, Mette Habekost, Camilla H Knudsen, Susanne H Buchholdt, Jinrong Huang, Fengping Xu, Xin Liu, Lars Bolund, Yonglun Luo, Poul Nissen, Fabia Febbraro, Mark Denham
The P-type ATPases family consists of ion and lipid transporters. Their unique diversity in function and expression is critical for normal development. In this study we investigated human pluripotent stem cells (hPSC) and different neural progenitor states to characterize the expression of the plasma membrane calcium ATPases (PMCAs) during human neural development and in mature mesencephalic dopaminergic (mesDA) neurons. Our RNA sequencing data identified a dynamic change in ATPase expression correlating with the differentiation time of the neural progenitors, which was independent of the neuronal progenitor type...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29458391/down-regulation-of-ghrelin-receptors-on-dopaminergic-neurons-in-the-substantia-nigra-contributes-to-parkinson-s-disease-like-motor-dysfunction
#14
Yukari Suda, Naoko Kuzumaki, Takefumi Sone, Michiko Narita, Kenichi Tanaka, Yusuke Hamada, Chizuru Iwasawa, Masahiro Shibasaki, Aya Maekawa, Miri Matsuo, Wado Akamatsu, Nobutaka Hattori, Hideyuki Okano, Minoru Narita
Ghrelin exerts a wide range of physiological actions throughout the body and appears to be a promising target for disease therapy. Endogenous ghrelin receptors (GHSRs) are present in extrahypothalamic sites including the substantia nigra pars compacta (SNc), which is related to phenotypic dysregulation or frank degeneration in Parkinson's disease (PD). Here we found a dramatic decrease in the expression of GHSR in PD-specific induced pluripotent stem cell (iPSC)-derived dopaminergic (DAnergic) neurons generated from patients carrying parkin gene (PARK2) mutations compared to those from healthy controls...
February 20, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29450981/nurr1-promotes-neurogenesis-of-dopaminergic-neuron-and-represses-inflammatory-factors-in-the-transwell-coculture-system-of-neural-stem-cells-and-microglia
#15
Xiaoxiang Chen, Yuan Qian, Xiangpeng Wang, Zhiwei Tang, Jiaotian Xu, Hai Lin, Zhiyong Yang, Xiaobin Song, Di Lu, Jiazhi Guo, Ligong Bian, Yu Li, Lei Zhou, Xingli Deng
INTRODUCTION: Neural stem cells (NSCs) are the most promising cells for cell replacement therapy for Parkinson's disease (PD). However, a majority of the transplanted NSCs differentiated into glial cells, thereby limiting the clinical application. Previous studies indicated that chronic neuroinflammation plays a vital role in the degeneration of midbrain DA (mDA) neurons, which suggested the developing potential of therapies for PD by targeting the inflammatory processes. Thus, Nurr1 (nuclear receptor-related factor 1), a transcription factor, has been referred to play a pivotal role in both the differentiation of dopaminergic neurons in embryonic stages and the maintenance of the dopaminergic phenotype throughout life...
February 15, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29428530/rotenone-exerts-developmental-neurotoxicity-in-a-human-brain-spheroid-model
#16
David Pamies, Katharina Block, Pierre Lau, Laura Gribaldo, Carlos Pardo, Paula Barreras, Lena Smirnova, Daphne Wiersma, Liang Zhao, Georgina Harris, Thomas Hartung, Helena T Hogberg
Growing concern suggests that some chemicals exert (developmental) neurotoxicity (DNT and NT) and are linked to the increase in incidence of autism, attention deficit and hyperactivity disorders. The high cost of routine tests for DNT and neurotoxicity (NT) assessment make it difficult to test the high numbers of existing chemicals. Thus, more cost effective neurodevelopmental models are needed. The use of induced pluripotent stem cells (iPSC) in combination with the emerging human 3D tissue culture platforms, present a novel tool to predicting and study human toxicity...
February 8, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29416637/liver-x-receptors-agonist-promotes-differentiation-of-rat-bone-marrow-derived-mesenchymal-stem-cells-into-dopaminergic-neuron-like-cells
#17
Oumei Cheng, Xiaoyan Tian, Ying Luo, Shaoshan Mai, Yang Yang, Shengnan Kuang, Qi Chen, Jie Ma, Beibei Chen, Rong Li, Lu Yang, Huan Li, Congli Hu, Jiahua Zhang, Zhihao Chen, Yuke Li, Hui Xia, Ying Xu, Junqing Yang
Dopaminergic (DA) neurons derived from bone marrow derived mesenchymal stem cells (BMSCs) maybe a valuable source for cell replacement therapy in Parkinson disease. Recent studies showed that new functions of LXR and their ligands have been proposed to prevent PD in the adult nervous system. The present study was designed to observe the effect of liver X receptors (LXR) agonist on differentiation of rat BMSCs into DA neurons. Expressions of the neuronal markers (Tuj1 and Nestin), the specific marker of DA neurons (tyrosine hydroxylase, TH), LXR α and LXR β were measured by immunocytochemical assay and TH/Tuj1 positive cells were determined by quantitative cell count analyses...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29411538/spion-mediated-mir-141-promotes-the-differentiation-of-huaescs-into-dopaminergic-neuron-like-cells-via-suppressing-lncrna-hotair
#18
Te Liu, Hu Zhang, Jiajia Zheng, Jiajia Lin, Yongyi Huang, Jiulin Chen, Zhihua Yu, Lihe Guo, Weidong Pan, Ying Xiong, Chuan Chen
In this study, a bioinformatics analysis and luciferase reporter assay revealed that microRNA-141 could silence the expression of lncRNA-HOTAIR by binding to specific sites on lncRNA-HOTAIR. We used superparamagnetic iron oxide nanoparticles (SPIONs) to mediate the high expression of microRNA-141 (SPIONs@miR-141) in human amniotic epithelial stem cells (HuAESCs), which was followed by the induction of the differentiation of HuAESCs into dopaminergic neuron-like cells (iDNLCs). qPCR, western blot, immunofluorescence staining and HPLC all suggested that SPION-mediated overexpression of miR-141 could promote an increased expression of brain-derived neurotrophic factor (BDNF), DAT and 5-TH in HuAESC-derived iDNLCs...
February 7, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29402177/in-vitro-modeling-of-leucine-rich-repeat-kinase-2-lrrk2-g2019s-mediated-parkinson-s-disease-pathology
#19
Scott C Vermilyea, Marina Emborg
Leucine-rich repeat kinase 2 (LRRK2) G2019S (glycine to serine) is the most common mutation associated with sporadic and familial Parkinson's disease (PD) with 80% penetrance by age 70. This mutation is found worldwide, with up to 40% of individuals in the North African Arab population carrying the mutation. Induced pluripotent stem cells (iPSCs) derived from fibroblasts of patients carrying the LRRK2 G2019S mutation have been a critical source of cells for generating dopaminergic neurons and studying G2019S-related pathology...
February 5, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29401731/bc-box-motif-mediated-neuronal-differentiation-of-somatic-stem-cells
#20
Hiroshi Kanno, Yuqun Xu, Taykua Miyakawa, Atsuhiko Kubo, Tetsuhiro Higashida, Nahoko Baily Kobayashi, Tetsuhiko Yoshida, Masaru Tanokura
Von Hippel-Lindau tumor suppressor protein (pVHL) functions to induce neuronal differentiation of neural stem/progenitor cells (NSCs) and skin-derived precursors (SKPs). Here we identified a neuronal differentiation domain (NDD) in pVHL. Neuronal differentiation of SKPs was induced by intracellular delivery of a peptide composed of the amino-acid sequences encoded by the NDD. Neuronal differentiation mediated by the NDD was caused by the binding between it and elongin C followed by Janus kinase-2 (JAK2) ubiquitination of JAK2 and inhibition of the JAK2/the signal transducer and activator of transcription-3(STAT)3 pathway...
February 5, 2018: International Journal of Molecular Sciences
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