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Parkinson disease and stem cell

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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
#1
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
#2
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
#3
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
#4
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...
July 17, 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
#5
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
#6
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
#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/28689993/mapt-genetic-variation-and-neuronal-maturity-alter-isoform-expression-affecting-axonal-transport-in-ipsc-derived-dopamine-neurons
#8
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
https://www.readbyqxmd.com/read/28685937/neuroimmunomodulatory-properties-of-dpscs-in-an-in-vitro-model-of-parkinson-s-disease
#9
Nareshwaran Gnanasegaran, Vijayendran Govindasamy, Vasudevan Mani, Noor Hayaty Abu Kasim
In neurodegenerative diseases, such as Alzheimer's and Parkinson's, microglial cell activation is thought to contribute to their degeneration by producing neurotoxic compounds. While dental pulp stem cells (DPSCs) have been regarded as the next possible cell source for cell replacement therapy (CRT), their actual role when exposed in such harsh environment remains elusive. In this study, the immunomodulatory behavior of DPSCs from human subjects was investigated in a coculture system consisting of neuron and microglia which were treated with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, which mimics the inflammatory conditions and contribute to degeneration of dopaminergic (DA-ergic) neurons...
July 6, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28677758/transcriptome-profiling-of-the-subventricular-zone-and-dentate-gyrus-in-an-animal-model-of-parkinson-s-disease
#10
Xin-Jie Bao, Geng-Chao Wang, Fu-Xing Zuo, Xue-Yuan Li, Jun Wu, Guo Chen, Wan-Chen Dou, Yi Guo, Qin Shen, Ren-Zhi Wang
Adult neurogenesis in the subventricular zone (SVZ), as well as in the subgranular zone contributes to brain maintenance and regeneration. In the adult brain, dopamine (DA) can regulate the endogenous neural stem cells within these two regions, while a DA deficit may affect neurogenesis. Notably, the factors that regulate in vivo neurogenesis in these subregions have not yet been fully characterized, particularly following DA depletion. In thi study, we performed RNA sequencing to investigate transcriptomic changes in the SVZ and dentate gyrus (DG) of mice in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...
September 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28673772/methyl-4-phenylpyridinium-mpp-differentially-affects-monoamine-release-and-re-uptake-in-murine-embryonic-stem-cell-derived-dopaminergic-and-serotonergic-neurons
#11
Yasmina Martí, Friederike Matthaeus, Thorsten Lau, Patrick Schloss
1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) is known to selectively damage dopaminergic (DA) cells in the substantia nigra and to produce symptoms which are alike to those observed in Parkinson's disease (PD). Based on the similarity between MPTP-induced neurotoxicity and PD-related neuropathology, application of MPTP or its metabolite methyl-4-phenylpyridinium (MPP+) was successfully established in experimental rodent models to study PD-related neurodegenerative events. MPP+ is taken up by the dopamine transporter (DAT) into DA neurons where it exerts its neurotoxic action on mitochondria by affecting complex I of the respiratory chain...
June 30, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28669622/smad4-is-essential-for-directional-progression-from-committed-neural-progenitor-cells-through-neuronal-differentiation-in-the-postnatal-mouse-brain
#12
Motoko Kawaguchi-Niida, Noriyuki Shibata, Yasuhide Furuta
Signaling by the TGFβ super-family, consisting of TGFβ/activin- and bone morphogenetic protein (BMP) branch pathways, is involved in the central nervous system patterning, growth, and differentiation during embryogenesis. Neural progenitor cells are implicated in various pathological conditions, such as brain injury, infarction, Parkinson's disease and Alzheimer's disease. However, the roles of TGFβ/BMP signaling in the postnatal neural progenitor cells in the brain are still poorly understood. We examined the functional contribution of Smad4, a key integrator of TGFβ/BMP signaling pathways, to the regulation of neural progenitor cells in the subventricular zone (SVZ)...
June 29, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28656059/parkin-knockout-inhibits-neuronal-development-via-regulation-of-proteasomal-degradation-of-p21
#13
Mi Hee Park, Hwa-Jeong Lee, Hye Lim Lee, Dong Ju Son, Jung Hoon Ju, Byung Kook Hyun, Sung Hee Jung, Ju-Kyoung Song, Dong Hun Lee, Chul Ju Hwang, Sang Bae Han, Sanghyeon Kim, Jin Tae Hong
PARK2 encodes for the E3 ubiquitin ligase parkin and is implicated in the development of Parkinson's disease (PD). Although the neuroprotective role of parkin is well known, the mechanism of PARK2's function in neural stem differentiation has not yet been thoroughly studied. Co-expressions network analysis showed that synaptosomal-associated protein 25 (SNAP-25) and brain-derived neurotrophic factor (BDNF) were positively correlated with parkin, but negatively correlated with p21 in human patient brain. We investigated a link between the ubiquitin E3 ligase parkin and proteasomal degradation of p21 for the control of neural stem cell differentiation...
2017: Theranostics
https://www.readbyqxmd.com/read/28650520/immature-midbrain-dopaminergic-neurons-derived-from-floor-plate-method-improve-cell-transplantation-therapy-efficacy-for-parkinson-s-disease
#14
Lifeng Qiu, Mei-Chih Liao, Allen K Chen, Shunhui Wei, Shaoping Xie, Shaul Reuveny, Zhi Dong Zhou, Walter Hunziker, Eng King Tan, Steve K W Oh, Li Zeng
Recent reports have indicated human embryonic stem cells-derived midbrain dopamine (mDA) neurons as proper cell resources for use in Parkinson's disease (PD) therapy. Nevertheless, no detailed and systematic study has been conducted to identify which differentiation stages of mDA cells are most suitable for transplantation in PD therapy. Here, we transplanted three types of mDA cells, DA progenitors (differentiated in vitro for 16 days [D16]), immature DA neurons (D25), and DA neurons (D35), into PD mice and found that all three types of cells showed high viability and strong neuronal differentiation in vivo...
June 26, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28641510/recent-advances-on-the-role-of-neurogenesis-in-the-adult-brain-therapeutic-potential-in-parkinson-s-and-alzheimer-s-diseases
#15
Khaled Salman Radad, Rudolf Moldzio, Mubarak Al-Shraim, Barbara Kranner, Christopher Krewenka, Wolf-Dieter Rausch
Generation of nascent functional neurons from neural stem cells in the adult brain has recently become largely accepted by the neuroscience community. In adult mammals including humans, the process of neurogenesis has been well documented in two brain regions; the subventricular zone of the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus. Some evidence has indicated neurogenesis in other regions of the adult mammalian brain such as the neocortex, cerebellum, striatum, amygdala and hypothalamus...
June 22, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28635509/induced-pluripotent-stem-cell-derived-dopaminergic-neurons-from-adult-common-marmoset-fibroblasts
#16
Scott C Vermilyea, Scott Guthrie, Michael Meyer, Kim Smuga-Otto, Katarina Braun, Sara Howden, James A Thomson, Su-Chun Zhang, Marina Emborg, Dr Thaddeus G Golos
The common marmoset monkey (Callithrix jacchus; Cj) is an advantageous nonhuman primate species for modeling age-related disorders, including Parkinson's disease, due to their shorter lifespan compared to macaques. Cj-derived induced pluripotent stem cells (Cj-iPSCs) from somatic cells are needed for in vitro disease modeling and testing regenerative medicine approaches. Here we report the development of a novel Cj-iPSC line derived from adult marmoset fibroblasts. The Cj-iPSCs showed potent pluripotency properties including development of mesodermal lineages in tumors after injection to immunocompromised mice, as well as ectoderm and endoderm lineages after in vitro differentiation regimens, demonstrating differentiated derivatives of all three embryonic layers...
June 21, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28592657/induced-pluripotent-stem-cell-models-of-lysosomal-storage-disorders
#17
REVIEW
Daniel K Borger, Benjamin McMahon, Tamanna Roshan Lal, Jenny Serra-Vinardell, Elma Aflaki, Ellen Sidransky
Induced pluripotent stem cells (iPSCs) have provided new opportunities to explore the cell biology and pathophysiology of human diseases, and the lysosomal storage disorder research community has been quick to adopt this technology. Patient-derived iPSC models have been generated for a number of lysosomal storage disorders, including Gaucher disease, Pompe disease, Fabry disease, metachromatic leukodystrophy, the neuronal ceroid lipofuscinoses, Niemann-Pick types A and C1, and several of the mucopolysaccharidoses...
June 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28591653/a-highly-efficient-human-pluripotent-stem-cell-microglia-model-displays-a-neuronal-co-culture-specific-expression-profile-and-inflammatory-response
#18
Walther Haenseler, Stephen N Sansom, Julian Buchrieser, Sarah E Newey, Craig S Moore, Francesca J Nicholls, Satyan Chintawar, Christian Schnell, Jack P Antel, Nicholas D Allen, M Zameel Cader, Richard Wade-Martins, William S James, Sally A Cowley
Microglia are increasingly implicated in brain pathology, particularly neurodegenerative disease, with many genes implicated in Alzheimer's, Parkinson's, and motor neuron disease expressed in microglia. There is, therefore, a need for authentic, efficient in vitro models to study human microglial pathological mechanisms. Microglia originate from the yolk sac as MYB-independent macrophages, migrating into the developing brain to complete differentiation. Here, we recapitulate microglial ontogeny by highly efficient differentiation of embryonic MYB-independent iPSC-derived macrophages then co-culture them with iPSC-derived cortical neurons...
June 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28589443/metformin-a-future-therapy-for-neurodegenerative-diseases
#19
REVIEW
Magdalena Markowicz-Piasecka, Joanna Sikora, Aleksandra Szydłowska, Agata Skupień, Elżbieta Mikiciuk-Olasik, Kristiina M Huttunen
Type 2 diabetes mellitus (T2DM) is a complex, chronic and progressive metabolic disease, which is characterized by relative insulin deficiency, insulin resistance, and high glucose levels in blood. Esteemed published articles and epidemiological data exhibit an increased risk of developing Alzheimer's disease (AD) in diabetic pateints. Metformin is the most frequently used oral anti-diabetic drug, which apart from hypoglycaemic activity, improves serum lipid profiles, positively influences the process of haemostasis, and possesses anti-inflammatory properties...
June 6, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28585381/modeling-parkinson-s-disease-with-induced-pluripotent-stem-cells-harboring-%C3%AE-synuclein-mutations
#20
Karamjit Singh Dolt, Fella Hammachi, Tilo Kunath
Parkinson's disease (PD) is a common neurodegenerative condition affecting more than 8 million people worldwide. Although, the majority of PD cases are sporadic in nature, there are a growing number of monogenic mutations identified to cause PD in a highly penetrant manner. Many of these familial mutations give rise to a condition that is clinically and neuropathologically similar, if not identical, to sporadic PD. Mutations in genes such as SNCA cause PD in an autosomal dominant manner and patients have motor and non-motor symptoms that are typical for sporadic PD...
July 2017: Brain Pathology
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