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Parkinson disease and stem cell

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https://www.readbyqxmd.com/read/28100850/molecular-characteristic-and-physiological-role-of-dopa-decarboxylase
#1
Joanna Guenter, Robert Lenartowski
The enzyme DOPA decarboxylase (aromatic-L-amino-acid decarboxylase, DDC) plays an important role in the dopaminergic system and participates in the uptake and decarboxylation of amine precursors in the peripheral tissues. Apart from catecholamines, DDC catalyses the biosynthesis of serotonin and trace amines. It has been shown that the DDC amino acid sequence is highly evolutionarily conserved across many species. The activity of holoenzyme is regulated by stimulation/blockade of membrane receptors, phosphorylation of serine residues, and DDC interaction with regulatory proteins...
December 31, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28096964/g-csf-for-mobilizing-transplanted-bone-marrow-stem-cells-in-rat-model-of-parkinson-s-disease
#2
Manouchehr Safari, Behnaz Jafari, Sam Zarbakhsh, Hamidreza Sameni, Abbas Ali Vafaei, Nasrin Khan Mohammadi, Laya Ghahari
OBJECTIVES: Granulocyte-colony stimulating factor (G-CSF) is used in clinical practice for the treatment of neutropenia and to stimulate generation of hematopoietic stem cells in bone marrow donors. In the present study, the ability of G-CSF in mobilizing exogenous bone marrow stem cells (BMSCs) from peripheral blood into the brain was tested. We for the first time injected a small amount of BMSCs through the tail vein. MATERIALS AND METHODS: We choose 25 male Wistar rats (200-250 g) were lesioned by 6-OHDA injected into the left substantia nigra, pars compacta (SNpc)...
December 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28096185/transcriptomic-profiling-of-purified-patient-derived-dopamine-neurons-identifies-convergent-perturbations-and-therapeutics-for-parkinson-s-disease
#3
Cynthia Sandor, Paul Robertson, Charmaine Lang, Andreas Heger, Heather Booth, Jane Vowles, Lorna Witty, Rory Bowden, Michele Hu, Sally A Cowley, Richard Wade-Martins, Caleb Webber
While induced pluripotent stem cell (iPSC) technologies enable the study of inaccessible patient cell types, cellular heterogeneity can confound the comparison of gene expression profiles between iPSC-derived cell lines. Here, we purified iPSC-derived human dopaminergic neurons (DaNs) using the intracellular marker, tyrosine hydroxylase. Once purified, the transcriptomic profiles of iPSC-derived DaNs appear remarkably similar to profiles obtained from mature post-mortem DaNs. Comparison of the profiles of purified iPSC-derived DaNs derived from Parkinson's disease (PD) patients carrying LRRK2 G2019S variants to controls identified significant functional convergence amongst differentially-expressed (DE) genes...
January 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28094018/single-cell-analysis-reveals-a-close-relationship-between-differentiating-dopamine-and-subthalamic-nucleus-neuronal-lineages
#4
Nigel Kee, Nikolaos Volakakis, Agnete Kirkeby, Lina Dahl, Helena Storvall, Sara Nolbrant, Laura Lahti, Åsa K Björklund, Linda Gillberg, Eliza Joodmardi, Rickard Sandberg, Malin Parmar, Thomas Perlmann
Stem cell engineering and grafting of mesencephalic dopamine (mesDA) neurons is a promising strategy for brain repair in Parkinson's disease (PD). Refinement of differentiation protocols to optimize this approach will require deeper understanding of mesDA neuron development. Here, we studied this process using transcriptome-wide single-cell RNA sequencing of mouse neural progenitors expressing the mesDA neuron determinant Lmx1a. This approach resolved the differentiation of mesDA and neighboring neuronal lineages and revealed a remarkably close relationship between developing mesDA and subthalamic nucleus (STN) neurons, while also highlighting a distinct transcription factor set that can distinguish between them...
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28094017/predictive-markers-guide-differentiation-to-improve-graft-outcome-in-clinical-translation-of-hesc-based-therapy-for-parkinson-s-disease
#5
Agnete Kirkeby, Sara Nolbrant, Katarina Tiklova, Andreas Heuer, Nigel Kee, Tiago Cardoso, Daniella Rylander Ottosson, Mariah J Lelos, Pedro Rifes, Stephen B Dunnett, Shane Grealish, Thomas Perlmann, Malin Parmar
Stem cell treatments for neurodegenerative diseases are expected to reach clinical trials soon. Most of the approaches currently under development involve transplantation of immature progenitors that subsequently undergo phenotypic and functional maturation in vivo, and predicting the long-term graft outcome already at the progenitor stage remains a challenge. Here, we took an unbiased approach to identify predictive markers expressed in dopamine neuron progenitors that correlate with graft outcome in an animal model of Parkinson's disease through gene expression analysis of >30 batches of grafted human embryonic stem cell (hESC)-derived progenitors...
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28091566/efficient-generation-of-hpsc-derived-midbrain-dopaminergic-neurons-in-a-fully-defined-scalable-3d-biomaterial-platform
#6
Maroof M Adil, Gonçalo M C Rodrigues, Rishikesh U Kulkarni, Antara T Rao, Nicole E Chernavsky, Evan W Miller, David V Schaffer
Pluripotent stem cells (PSCs) have major potential as an unlimited source of functional cells for many biomedical applications; however, the development of cell manufacturing systems to enable this promise faces many challenges. For example, there have been major recent advances in the generation of midbrain dopaminergic (mDA) neurons from stem cells for Parkinson's Disease (PD) therapy; however, production of these cells typically involves undefined components and difficult to scale 2D culture formats. Here, we used a fully defined, 3D, thermoresponsive biomaterial platform to rapidly generate large numbers of action-potential firing mDA neurons after 25 days of differentiation (~40% tyrosine hydroxylase (TH) positive, maturing into 25% cells exhibiting mDA neuron-like spiking behavior)...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28079995/effects-of-cell-cycle-phases-on-the-induction-of-dental-pulp-stem-cells-toward-dopaminergic-like-cells
#7
Nareshwaran Gnanasegaran, Vijayendran Govindasamy, Premasangery Kathirvaloo, Sabri Musa, Noor Hayaty Abu Kasim
Parkinson's disease (PD) is characterized by tremors and cognitive issues, and is due to the death of dopaminergic (DA-ergic) neurons in brain circuits that are responsible for producing neurotransmitter dopamine (DA). Currently, cell replacement therapies are underway to overcome existing therapeutic approaches such as drug treatments and electrical stimulation. Among the widely available sources, dental pulp stem cells from deciduous teeth (DPSC) have gained popularity due to their neural crest origin and inherent propensity toward neuronal lineage...
January 12, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28066829/the-multifaceted-role-of-nrf2-in-mitochondrial-function
#8
REVIEW
Kira M Holmström, Rumen V Kostov, Albena T Dinkova-Kostova
The transcription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2) is the master regulator of the cellular redox homeostasis. Nrf2 target genes comprise of a large network of antioxidant enzymes, proteins involved in xenobiotic detoxification, repair and removal of damaged proteins, inhibition of inflammation, as well as other transcription factors. In recent years it has emerged that as part of its role as a regulator of cytoprotective gene expression, Nrf2 impacts mitochondrial function. Increased Nrf2 activity defends against mitochondrial toxins...
December 2016: Curr Opin Toxicol
https://www.readbyqxmd.com/read/28061349/seq-ing-markers-of-midbrain-dopamine-neurons
#9
Teresia Osborn, Penelope J Hallett
Transplantation of human pluripotent stem cell-derived dopaminergic neurons is a promising approach to treating Parkinson's disease. In this issue of Cell Stem Cell, Kee et al. (2017) and Kirkeby et al. (2017) identify specific markers of midbrain dopaminergic progenitors to improve their derivation and predict dopamine neuron content after engraftment.
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28057485/efficient-induction-of-dopaminergic-neuron-differentiation-from-induced-pluripotent-stem-cells-reveals-impaired-mitophagy-in-park2-neurons
#10
Sadafumi Suzuki, Wado Akamatsu, Fumihiko Kisa, Takefumi Sone, Kei-Ichi Ishikawa, Naoko Kuzumaki, Hiroyuki Katayama, Atsushi Miyawaki, Nobutaka Hattori, Hideyuki Okano
Patient-specific induced pluripotent stem cells (iPSCs) show promise for use as tools for in vitro modeling of Parkinson's disease. We sought to improve the efficiency of dopaminergic (DA) neuron induction from iPSCs by the using surface markers expressed in DA progenitors to increase the significance of the phenotypic analysis. By sorting for a CD184(high)/CD44(-) fraction during neural differentiation, we obtained a population of cells that were enriched in DA neuron precursor cells and achieved higher differentiation efficiencies than those obtained through the same protocol without sorting...
January 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28043116/current-opinion-on-the-role-of-neurogenesis-in-the-therapeutic-strategies-for-alzheimer-disease-parkinson-disease-and-ischemic-stroke-considering-neuronal-voiding-function
#11
REVIEW
Myung-Hoon Han, Eun-Hye Lee, Seong-Ho Koh
Neurological diseases such as Alzheimer, Parkinson, and ischemic stroke have increased in occurrence and become important health issues throughout the world. There is currently no effective therapeutic strategy for addressing neurological deficits after the development of these major neurological disorders. In recent years, it has become accepted that adult neural stem cells located in the subventricular and subgranular zones have the ability to proliferate and differentiate in order to replace lost or damaged neural cells...
December 2016: International Neurourology Journal
https://www.readbyqxmd.com/read/28017799/x-linked-dystonia-parkinsonism-patient-cells-exhibit-altered-signaling-via-nuclear-factor-kappa-b
#12
Christine A Vaine, David Shin, Christina Liu, William Hendriks, Jyotsna Dhakal, Kyle Shin, Nutan Sharma, Cristopher Bragg
X-linked Dystonia-Parkinsonism (XDP) is a progressive neurodegenerative disease involving the loss of medium spiny neurons within the striatum. An XDP-specific haplotype has been identified, consisting of seven sequence variants which cluster around the human TAF1 gene, but a direct relationship between any of these variants and disease pathogenesis has not yet been demonstrated. Because the pathogenic gene lesion remains unclear, it has been difficult to predict cellular pathways which are affected in XDP cells...
December 22, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27987378/in-vitro-differentiation-of-neural-stem-cells-derived-from-human-olfactory-bulb-into-dopaminergic-like-neurons
#13
Rafieh Alizadeh, Gholamreza Hassanzadeh, Mohammad Taghi Joghataei, Mansoureh Soleimani, Fatemeh Moradi, Shahram Mohammadpour, Jahangir Ghorbani, Ali Safavi, Maryam Sarbishegi, Vahid Pirhajati Mahabadi, Leila Alizadeh, Mahmoudreza Hadjighassem
Obtaining new accessible source of neuronal stem cells that can be used in Parkinson's disease cell transplant is the aim of this research. The human olfactory bulb contains neural stem cells (NSCs) that are responsible for the neurogenesis in the brain and the replacement of damaged cellular components throughout life. NSCs are capable of differentiating into neuronal and glial cells. We isolated NSCs from brain-death donor's olfactory bub and differentiate them to dopaminergic neurons. The obtained olfactory bulb tissues were cultured in DMEM12, B27 supplemented with bFGF, EGF, and LIF...
December 17, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27981499/direct-conversion-of-somatic-cells-into-induced-neurons
#14
REVIEW
Na An, Huiming Xu, Wei-Qiang Gao, Hao Yang
The progressive loss and degeneration of neurons in the central nervous system (CNS), as a result of traumas or diseases including Alzheimer's, Parkinson's, Huntington's disease, stroke, and traumatic injury to the brain and spinal cord, can usually have devastating effects on quality of life. The current strategies available for treatments are described including drug delivery, surgery, electrical stimulation, and cell-based tissue engineering approaches. However, apart from cell-based therapy, other attempts are limited in improving clinical outcomes...
December 16, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27977132/mk-801-dizocilpine-regulates-multiple-steps-of-adult-hippocampal-neurogenesis-and-alters-psychological-symptoms-via-wnt-%C3%AE-catenin-signaling-in-parkinsonian-rats
#15
Sonu Singh, Akanksha Mishra, Neha Srivastava, Shubha Shukla
Adult hippocampal neurogenesis is directly involved in regulation of stress, anxiety, and depression that are commonly observed nonmotor symptoms in Parkinson's disease (PD). These symptoms do not respond to pharmacological dopamine replacement therapy. Excitotoxic damage to neuronal cells by N-methyl-d-aspartate (NMDA) receptor activation is also a major contributing factor in PD development, but whether it regulates hippocampal neurogenesis and nonmotor symptoms in PD is yet unexplored. Herein, for the first time, we studied the effect of MK-801, an NMDA receptor antagonist, on adult hippocampal neurogenesis and behavioral functions in 6-OHDA (6-hydroxydopamine) induced rat model of PD...
December 15, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27975167/lrrk2-expression-is-deregulated-in-fibroblasts-and-neurons-from-parkinson-patients-with-mutations-in-pink1
#16
Garikoitz Azkona, Rakel López de Maturana, Patricia Del Rio, Amaya Sousa, Nerea Vazquez, Amaia Zubiarrain, Daniel Jimenez-Blasco, Juan P Bolaños, Blas Morales, Georg Auburger, José Matias Arbelo, Rosario Sánchez-Pernaute
Mutations in PINK1 (PARK6), a serine/threonine kinase involved in mitochondrial homeostasis, are associated with early onset Parkinson's disease. Fibroblasts from Parkinson's disease patients with compound heterozygous mutations in exon 7 (c.1488 + 1G > A; c.1252_1488del) showed no apparent signs of mitochondrial impairment. To elucidate changes primarily caused by lack of functional PINK1, we over-expressed wild-type PINK1, which induced a significant downregulation of LRRK2 (PARK8). Indeed, we found that LRRK2 protein basal levels were significantly higher in the mutant PINK1 fibroblasts...
December 14, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27943459/protective-roles-of-melatonin-in-central-nervous-system-diseases-by-regulation-of-neural-stem-cells
#17
REVIEW
Xin Yu, Zheng Li, Heyi Zheng, Jeffery Ho, Matthew T V Chan, William Ka Kei Wu
Neural stem cells (NSCs) are immature precursors of the central nervous system (CNS), with self-renewal and multipotential differentiation abilities. Their proliferation and differentiation are dynamically regulated by hormonal and local factors. Alteration in neurogenesis is associated with many neurological disorders. Increasing evidence suggests that modulation of NSCs can be a promising therapeutic approach for neural injury and neurodegenerative disorders. Melatonin, a pineal gland-derived hormone, regulates the neuroimmuno-endocrine axis and is functionally important to the circadian rhythm, tumour suppression and immunity...
December 12, 2016: Cell Proliferation
https://www.readbyqxmd.com/read/27934590/generation-of-an-isogenic-gene-corrected-ipsc-line-from-a-pre-symptomatic-28-year-old-woman-with-an-r406w-mutation-in-the-microtubule-associated-protein-tau-mapt-gene
#18
Natakarn Nimsanor, Ulla Poulsen, Mikkel A Rasmussen, Christian Clausen, Ulrike A Mau-Holzmann, Jørgen E Nielsen, Troels T Nielsen, Poul Hyttel, Bjørn Holst, Benjamin Schmid
Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau) gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required cell type. Furthermore, gene-editing approaches allow generating isogenic gene-corrected controls that can be used as a very specific control...
September 28, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27934586/generation-of-an-isogenic-gene-corrected-ipsc-line-from-a-symptomatic-59-year-old-female-patient-with-frontotemporal-dementia-caused-by-an-r406w-mutation-in-the-microtubule-associated-protein-tau-mapt-gene
#19
Natakarn Nimsanor, Ulla Poulsen, Mikkel A Rasmussen, Christian Clausen, Ulrike A Mau-Holzmann, Jørgen E Nielsen, Troels T Nielsen, Poul Hyttel, Bjørn Holst, Benjamin Schmid
Frontotemporal dementia with parkinsonism linked to chromosome 17q21.2 (FTDP-17) is an autosomal-dominant neurodegenerative disorder. Mutations in the MAPT (microtubule-associated protein tau) gene can cause FTDP-17, but the underlying pathomechanisms of the disease are still unknown. Induced pluripotent stem cells (iPSCs) hold great promise to model FTDP-17 as such cells can be differentiated in vitro to the required cell type. Furthermore, gene-editing approaches allow generating isogenic gene-corrected controls that can be used as a very specific control...
September 28, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27931506/neural-stem-cells-derived-from-human-parthenogenetic-stem-cells-engraft-and-promote-recovery-in-a-nonhuman-primate-model-of-parkinsons-disease
#20
Rodolfo Gonzalez, Ibon Garitaonandia, Maxim Poustovoitov, Tatiana Abramihina, Caleb McEntire, Ben Culp, Jordan Attwood, Alexander Noskov, Trudy Christiansen-Weber, Marwa Khater, Sergio Mora-Castilla, Cuong To, Andrew Crain, Glenn Sherman, Andrey Semechkin, Louise C Laurent, John D Elsworth, John Sladek, Evan Y Snyder, D Eugene Redmond, Russell A Kern
Cell therapy has attracted considerable interest as a promising therapeutic alternative for patients with Parkinsons disease (PD). Clinical studies have shown that grafted fetal neural tissue can achieve considerable biochemical and clinical improvements in PD. However, the source of fetal tissue grafts is limited and ethically controversial. Human parthenogenetic stem cells offer a good alternative because they are derived from unfertilized oocytes without destroying potentially viable human embryos and can be used to generate an unlimited supply of neural cells for transplantation...
November 2016: Cell Transplantation
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