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Parkinson disease and stem cell

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https://www.readbyqxmd.com/read/29766664/tissue-engineered-nigrostriatal-pathway-for-treatment-of-parkinson-s-disease
#1
Laura A Struzyna, Kevin D Browne, Zachary D Brodnik, Justin C Burrell, James P Harris, H Isaac Chen, John A Wolf, Kate V Panzer, James Lim, John E Duda, Rodrigo A España, D Kacy Cullen
The classic motor deficits of Parkinson's disease are caused by degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in the loss of their long-distance axonal projections that modulate the striatum. Current treatments only minimize the symptoms of this disconnection as there is no approach capable of replacing the nigrostriatal pathway. We are applying micro-tissue engineering techniques to create living, implantable constructs that mimic the architecture and function of the nigrostriatal pathway...
May 15, 2018: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29756519/adipose-derived-stem-cells-stimulated-with-n-butylidenephthalide-exhibit-therapeutic-effects-in-a-mouse-model-of-parkinson-s-disease
#2
Kang Chi, Ru-Huei Fu, Yu-Chuen Huang, Shih-Yin Chen, Ching-Ju Hsu, Shinn-Zong Lin, Chi-Tang Tu, Li-Hsun Chang, Ping-An Wu, Shih-Ping Liu
Parkinson's disease (PD) causes motor dysfunction and dopaminergic cell death. Drug treatments can effectively reduce symptoms but often cause unwanted side effects. Stem cell therapies using cell replacement or indirect beneficial secretomes have recently emerged as potential therapeutic strategies. Although various types of stem cells have been proposed as possible candidates, adipose-derived stem cells (ADSCs) are easily obtainable, more abundant, less ethically disputed, and able to differentiate into multiple cell lineages...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29735433/glycosphingolipid-levels-and-glucocerebrosidase-activity-are-altered-in-normal-aging-of-the-mouse-brain
#3
Penelope J Hallett, Mylene Huebecker, Oeystein R Brekk, Elizabeth B Moloney, Emily M Rocha, David A Priestman, Frances M Platt, Ole Isacson
Aging is the predominant risk factor for both genetic and sporadic Parkinson's disease (PD). The majority of PD cases are nonfamilial, and the connection between aging and PD-associated genes is not well understood. Haploinsufficiency of the GBA gene, leading to a reduction in glucocerebrosidase (GCase) activity, is one of the most common genetic risk factors for PD. Furthermore, GCase activity is also reduced in brain regions of sporadic PD patients, with a corresponding accumulation of its glycosphingolipid (GSL) substrates...
March 29, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29722301/collagen-for-brain-repair-therapeutic-perspectives
#4
REVIEW
Buket Ucar, Christian Humpel
Biomaterials have increasingly become a focus of research on neuroprotection and neuroregeneration. Collagen, in terms of brain repair, presents many advantages such as being remarkably biocompatible, biodegradable, versatile and non-toxic. Collagen can be used to form injectable scaffolds and micro/nano spheres in order to: (i) locally release therapeutic factors with the aim of protecting degenerating neurons in neurodegenerative conditions such as Alzheimer's or Parkinson's diseases, (ii) encapsulate stem cells for safe delivery, (iii) encapsulate genetically modified cells to provide a long term source of trophic factors, (iv) fill in the voids from injury to serve as a structural support and provide a permissive microenvironment to promote axonal growth...
April 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29701146/role-of-melatonin-in-the-inflammatory-process-and-its-therapeutic-potential
#5
Livia Carrascal, Pedro Nunez-Abades, Antonio Ayala, Mercedes Cano
Melatonin is an indolamine synthesized and secreted by the pineal gland along with other sources including immune system cells, the brain, skin and the gastrointestinal tract. Growing interest in this compound as a potential therapeutic agent in several diseases stems from its pleiotropic effects. Thus, melatonin plays a key role in various physiological activities that include regulation of circadian rhythms, immune responses, the oxidative process, apoptosis or mitochondrial homeostasis. Most of these processes are altered during inflammatory pathologies, among which neurodegenerative and bowel diseases stand out...
April 25, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29692195/exosomes-and-stem-cells-in-degenerative-disease-diagnosis-and-therapy
#6
Yu-Hsun Chang, Kung-Chi Wu, Horng-Jyh Harn, Shinn-Zong Lin, Dah-Ching Ding
Stroke can cause death and disability, resulting in a huge burden on society. Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by motor dysfunction. Osteoarthritis (OA) is a progressive degenerative joint disease characterized by cartilage destruction and osteophyte formation in the joints. Stem cell therapy may provide a biological treatment alternative to traditional pharmacological therapy. Mesenchymal stem cells (MSCs) are preferred because of their differentiation ability and possible derivation from many adult tissues...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29688812/nitration-of-microtubules-blocks-axonal-mitochondrial-transport-in-a-human-pluripotent-stem-cell-model-of-parkinson-s-disease
#7
Morgan G Stykel, Kayla Humphries, Mathew P Kirby, Chris Czaniecki, Tinya Wang, Tammy Ryan, Vladimir Bamm, Scott D Ryan
Neuronal loss in Parkinson's disease (PD) is associated with aberrant mitochondrial function in dopaminergic (DA) neurons of the substantia nigra pars compacta. An association has been reported between PD onset and exposure to mitochondrial toxins, including the agrochemicals paraquat (PQ), maneb (MB), and rotenone (Rot). Here, with the use of a patient-derived stem cell model of PD, allowing comparison of DA neurons harboring a mutation in the α-synuclein (α-syn) gene ( SNCA-A53T) against isogenic, mutation-corrected controls, we describe a novel mechanism whereby NO, generated from SNCA-A53T mutant neurons exposed to Rot or PQ/MB, inhibits anterograde mitochondrial transport through nitration of α-tubulin (α-Tub)...
April 24, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29686602/advancing-stem-cell-models-of-alpha-synuclein-gene-regulation-in-neurodegenerative-disease
#8
REVIEW
Desiree A Piper, Danuta Sastre, Birgitt Schüle
Alpha-synuclein ( non A4 component of amyloid precursor, SNCA, NM_000345.3 ) plays a central role in the pathogenesis of Parkinson's disease (PD) and related Lewy body disorders such as Parkinson's disease dementia, Lewy body dementia, and multiple system atrophy. Since its discovery as a disease-causing gene in 1997, alpha-synuclein has been a central point of scientific interest both at the protein and gene level. Mutations, including copy number variants, missense mutations, short structural variants, and single nucleotide polymorphisms, can be causative for PD and affect conformational changes of the protein, can contribute to changes in expression of alpha-synuclein and its isoforms, and can influence regulation of temporal as well as spatial levels of alpha-synuclein in different tissues and cell types...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29669468/inducible-alpha-synuclein-expression-affects-human-neural-stem-cell-behavior
#9
Jacopo Zasso, Ahmed Mastad, Alessandro Cutarelli, Luciano Conti
Converging evidence suggest that levels of alpha-Synuclein (aSyn) expression play a critical role in Parkinson's disease (PD). Several mutations of the SNCA gene, encoding for aSyn have been associated to either the familial or the sporadic forms of PD. Nonetheless, the mechanism underlying wild type aSyn-mediated neurotoxicity in neuronal cells as well as its specific driving role in PD pathogenesis has yet to be fully clarified. In this view, the development of proper in vitro cellular systems is a crucial step...
April 19, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29666786/modeling-neuropsychiatric-and-neurodegenerative-diseases-with-induced-pluripotent-stem-cells
#10
REVIEW
Elizabeth A LaMarca, Samuel K Powell, Schahram Akbarian, Kristen J Brennand
Human-induced pluripotent stem cells (hiPSCs) have revolutionized our ability to model neuropsychiatric and neurodegenerative diseases, and recent progress in the field is paving the way for improved therapeutics. In this review, we discuss major advances in generating hiPSC-derived neural cells and cutting-edge techniques that are transforming hiPSC technology, such as three-dimensional "mini-brains" and clustered, regularly interspersed short palindromic repeats (CRISPR)-Cas systems. We examine specific examples of how hiPSC-derived neural cells are being used to uncover the pathophysiology of schizophrenia and Parkinson's disease, and consider the future of this groundbreaking research...
2018: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/29653250/pluripotent-stem-cell-based-therapy-for-parkinson-s-disease-current-status-and-future-prospects
#11
REVIEW
Kai-C Sonntag, Bin Song, Nayeon Lee, Jin Hyuk Jung, Young Cha, Pierre Leblanc, Carolyn Neff, Sek Won Kong, Bob S Carter, Jeffrey Schweitzer, Kwang-Soo Kim
Parkinson's disease (PD) is one of the most common neurodegenerative disorders, which affects about 0.3% of the general population. As the population in the developed world ages, this creates an escalating burden on society both in economic terms and in quality of life for these patients and for the families that support them. Although currently available pharmacological or surgical treatments may significantly improve the quality of life of many patients with PD, these are symptomatic treatments that do not slow or stop the progressive course of the disease...
April 11, 2018: Progress in Neurobiology
https://www.readbyqxmd.com/read/29615705/gdnf-expressing-macrophages-mitigate-loss-of-dopamine-neurons-and-improve-parkinsonian-symptoms-in-mitopark-mice
#12
Cang Chen, Xiuhua Li, Guo Ge, Jingwei Liu, K C Biju, Suzette D Laing, Yusheng Qian, Cori Ballard, Zhixu He, Eliezer Masliah, Robert A Clark, Jason C O'Connor, Senlin Li
Glial cell line-derived neurotrophic factor (GDNF) is the most potent neuroprotective agent tested in cellular and animal models of Parkinson's disease (PD). However, CNS delivery of GDNF is restricted by the blood-brain barrier (BBB). Using total body irradiation as transplant preconditioning, we previously reported that hematopoietic stem cell (HSC) transplantation (HSCT)-based macrophage-mediated gene therapy could deliver GDNF to the brain to prevent degeneration of nigrostriatal dopamine (DA) neurons in an acute murine neurotoxicity model...
April 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29604226/stem-cell-modeling-of-mitochondrial-parkinsonism-reveals-key-functions-of-opa1
#13
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/29593485/-till-death-do-us-part-a-potential-irreversible-link-between-aberrant-cell-cycle-control-and-neurodegeneration-in-the-adult-olfactory-bulb
#14
REVIEW
Saad Omais, Carine Jaafar, Noël Ghanem
Adult neurogenesis (AN) is an ongoing developmental process that generates newborn neurons in the olfactory bulb (OB) and the hippocampus (Hi) throughout life and significantly contributes to brain plasticity. Adult neural stem and progenitor cells (aNSPCs) are relatively limited in number and fate and are spatially restricted to the subventricular zone (SVZ) and the subgranular zone (SGZ). During AN, the distinct roles played by cell cycle proteins extend beyond cell cycle control and constitute key regulatory mechanisms involved in neuronal maturation and survival...
2018: Frontiers in Neuroscience
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
#15
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/29576501/intrastriatal-transplantation-of-stem-cells-from-human-exfoliated-deciduous-teeth-reduces-motor-defects-in-parkinsonian-rats
#16
Nan Zhang, Xianjie Lu, Shichao Wu, Xueli Li, Jing Duan, Chao Chen, Wei Wang, Hao Song, Jiabei Tong, Sen Li, Yanming Liu, Xinjiang Kang, Xuexiang Wang, Fabin Han
BACKGROUND: This study explored the neural differentiation and therapeutic effects of stem cells from human exfoliated deciduous teeth (SHED) in a rat model of Parkinson's disease (PD). METHODS: The SHED were isolated from fresh dental pulp and were induced to differentiate to neurons and dopamine neurons by inhibiting similar mothers against dpp (SMAD) signaling with Noggin and increase conversion of dopamine neurons from SHED with CHIR99021, Sonic Hedgehog (SHH) and FGF8 in vitro...
March 22, 2018: Cytotherapy
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
#17
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
#18
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/29564126/induced-pluripotent-stem-cells-in-rat-models-of-parkinson-s-disease-a-systematic-review-and-meta-analysis
#19
Yunxia Zhang, Meiling Ge, Qiukui Hao, Birong Dong
The effects of induced pluripotent stem cells (iPSCs) in 6-hydroxydopamine-lesioned rat models of Parkinson's disease (PD) have been evaluated in multiple studies. However, the results evaluating the effectiveness of iPSCs in animal models of PD are mixed, primarily due to their low statistical power. In the current study, a meta-analysis was performed to describe the treatment effect of unsorted iPSCs on behavioral testing in experimental rat models of PD. Databases searched included PubMed, EMBASE, MEDLINE and the Cochrane Library from inception to March 2017...
March 2018: Biomedical Reports
https://www.readbyqxmd.com/read/29562865/regulatable-lentiviral-hematopoietic-stem-cell-gene-therapy-in-a-mouse-model-of-parkinson-s-disease
#20
Guo Ge, Cang Chen, Michael James Guderyon, Jingwei Liu, Zhixu He, Yanni Yu, Robert A Clark, Senlin Li
Glial cell line-derived neurotrophic factor (GDNF) exhibits potent neuroprotective properties in preclinical models of Parkinson's disease (PD), but challenges in GDNF delivery have been reported from clinical trials. To address this barrier, we developed a hematopoietic stem cell transplantation (HSCT) -based macrophage-mediated GDNF therapy platform. Here we introduced a regulatable lentiviral vector (LV-MSP-Tet-Off-hGDNF) in order to allow the expression of human GDNF to be adjusted or stopped by oral administration of doxycycline (Dox)...
March 21, 2018: Stem Cells and Development
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