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Parkinson disease and stem cell

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https://www.readbyqxmd.com/read/27885887/cell-therapies-for-parkinson-s-disease-how-far-have-we-come
#1
Thomas B Stoker, Roger A Barker
Over the past three decades, significant progress has been made in the development of potential regenerative cell-based therapies for neurodegenerative disease, with most success being seen in Parkinson's disease. Cell-based therapies face many challenges including ethical considerations, potential for immune-mediated rejection with allogeneic and xenogeneic tissue, pathological spread of protein-related disease into the grafted tissue as well as the risk of graft overgrowth and tumorigenesis in stem cell-derived transplants...
December 2016: Regenerative Medicine
https://www.readbyqxmd.com/read/27863501/mutations-in-lrrk2-impair-nf-%C3%AE%C2%BAb-pathway-in-ipsc-derived-neurons
#2
Rakel López de Maturana, Valérie Lang, Amaia Zubiarrain, Amaya Sousa, Nerea Vázquez, Ana Gorostidi, Julio Águila, Adolfo López de Munain, Manuel Rodríguez, Rosario Sánchez-Pernaute
BACKGROUND: Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to both familial and idiopathic forms of Parkinson's disease (PD). Neuroinflammation is a key event in neurodegeneration and aging, and there is mounting evidence of LRRK2 involvement in inflammatory pathways. In a previous study, we described an alteration of the inflammatory response in dermal fibroblasts from PD patients expressing the G2019S and R1441G mutations in LRRK2. METHODS: Taking advantage of cellular reprogramming, we generated induced pluripotent stem cell (iPSC) lines and neurons thereafter, harboring LRRK2(G2019S) and LRRK2(R1441G) mutations...
November 18, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27842480/mesenchymal-stem-cells-as-a-source-of-dopaminergic-neurons-a-potential-cell-based-therapy-for-parkinson-s-disease
#3
Katari Venkatesh, Dwaipayan Sen
Cell repair/replacing strategies for neurodegenerative diseases such as Parkinson's disease depend on well-characterized dopaminergic neuronal candidates that are healthy and show promising effect in the rejuvenation of degenerated area of the brain. Therefore, it is imperative to develop innovative therapeutic strategies that replace damaged neurons with new/functional dopaminergic neurons. Although several research groups have reported the generation of neural precursors/neurons from human/mouse embryonic stem cells and mesenchymal stem cells, the latter is considered to be an attractive therapeutic candidate because of its high capacity for self-renewable, no adverse effect to allogeneic versus autologous transplants, high ethical acceptance and no teratoma formation...
November 14, 2016: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/27831631/stem-cells-differentiation-and-probing-their-therapeutic-applications-in-hematological-disorders-a-critical-review
#4
F Ali, S Taresh, M Al-Nuzaily, P L Mok, A Ismail, S Ahmad
Numerous lines of evidence support that bone marrow is a rich source of stem cells that can be used for research purposes and to treat some complex blood diseases and cancers. Stem cells are a potential source for regenerative medicine and tissue replacement after injury or disease, and mother cells that possess the capacity to become any type of cell in the body. They are cells without specific structure and characterized by their ability to self-renew or multiply while maintaining the potential to develop into other types of cells...
October 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27830492/transcranial-magnetic-stimulation-for-the-assessment-of-neurodegenerative-disease
#5
REVIEW
Steve Vucic, Matthew C Kiernan
Transcranial magnetic stimulation (TMS) is a noninvasive technique that has provided important information about cortical function across an array of neurodegenerative disorders, including Alzheimer's disease, frontotemporal dementia, Parkinson's disease, and related extrapyramidal disorders. Application of TMS techniques in neurodegenerative diseases has provided important pathophysiological insights, leading to the development of pathogenic and diagnostic biomarkers that could be used in the clinical setting and therapeutic trials...
November 9, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27821734/role-of-sulfiredoxin-as-a-peroxiredoxin-2-denitrosylase-in-human-ipsc-derived-dopaminergic-neurons
#6
Carmen R Sunico, Abdullah Sultan, Tomohiro Nakamura, Nima Dolatabadi, James Parker, Bing Shan, Xuemei Han, John R Yates, Eliezer Masliah, Rajesh Ambasudhan, Nobuki Nakanishi, Stuart A Lipton
Recent studies have pointed to protein S-nitrosylation as a critical regulator of cellular redox homeostasis. For example, S-nitrosylation of peroxiredoxin-2 (Prx2), a peroxidase widely expressed in mammalian neurons, inhibits both enzymatic activity and protective function against oxidative stress. Here, using in vitro and in vivo approaches, we identify a role and reaction mechanism of the reductase sulfiredoxin (Srxn1) as an enzyme that denitrosylates (thus removing -SNO) from Prx2 in an ATP-dependent manner...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27817014/fibroblast-like-cells-as-an-effective-feeder-for-the-cultivation-and-derivation-of-new-lines-of-human-induced-pluripotent-stem-cells
#7
E V Novosadova, E S Manuilova, E L Arsenyeva, I A Grivennikov, N F Myasoedov
Induced pluripotent stem cells (iPSCs) can be a highly informative model of hereditary and sporadic human diseases. In the future, such cells can be used in substitution and regenerative therapy of a wide range of diseases and for the treatment of injuries and burns. The ability of iPSCs derived from patients with Parkinson's disease to differentiate into fibroblast-like cells (derivatives) was studied. It was found that these cells can serve as an effective feeder layer not only to maintain the pluripotency of allogenic and autologous iPSCs but also to derive new iPSC lines...
September 2016: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27815842/neurotrophin-signaling-and-stem-cells-implications-for-neurodegenerative-diseases-and-stem-cell-therapy
#8
REVIEW
Subrata Pramanik, Yanuar Alan Sulistio, Klaus Heese
Neurotrophins (NTs) are members of a neuronal growth factor protein family whose action is mediated by the tropomyosin receptor kinase (TRK) receptor family receptors and the p75 NT receptor (p75NTR), a member of the tumor necrosis factor (TNF) receptor family. Although NTs were first discovered in neurons, recent studies have suggested that NTs and their receptors are expressed in various types of stem cells mediating pivotal signaling events in stem cell biology. The concept of stem cell therapy has already attracted much attention as a potential strategy for the treatment of neurodegenerative diseases (NDs)...
November 5, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27812199/leucine-rich-repeat-kinase-2-influences-fate-decision-of-human-monocytes-differentiated-from-induced-pluripotent-stem-cells
#9
Anna Speidel, Sandra Felk, Peter Reinhardt, Jared Sterneckert, Frank Gillardon
Mutations in Leucine-rich repeat kinase 2 (LRRK2) are strongly associated with familial Parkinson's disease (PD). High expression levels in immune cells suggest a role of LRRK2 in regulating the immune system. In this study, we investigated the effect of the LRRK2 (G2019S) mutation in monocytes, using a human stem cell-derived model expressing LRRK2 at endogenous levels. We discovered alterations in the differentiation pattern of LRRK2 mutant, compared to non-mutant isogenic controls, leading to accelerated monocyte production and a reduction in the non-classical CD14+CD16+ monocyte subpopulation in the LRRK2 mutant cells...
2016: PloS One
https://www.readbyqxmd.com/read/27810402/impact-of-intermittent-fasting-on-health-and-disease-processes
#10
REVIEW
Mark P Mattson, Valter D Longo, Michelle Harvie
Humans in modern societies typically consume food at least three times daily, while laboratory animals are fed ad libitum. Overconsumption of food with such eating patterns often leads to metabolic morbidities (insulin resistance, excessive accumulation of visceral fat, etc.), particularly when associated with a sedentary lifestyle. Because animals, including humans, evolved in environments where food was relatively scarce, they developed numerous adaptations that enabled them to function at a high level, both physically and cognitively, when in a food-deprived/fasted state...
October 31, 2016: Ageing Research Reviews
https://www.readbyqxmd.com/read/27798097/genetic-and-pharmacological-correction-of-aberrant-dopamine-synthesis-using-patient-ipscs-with-bh4-metabolism-disorders
#11
Taizo Ishikawa, Keiko Imamura, Takayuki Kondo, Yasushi Koshiba, Satoshi Hara, Hiroshi Ichinose, Mahoko Furujo, Masako Kinoshita, Tomoko Oeda, Jun Takahashi, Ryosuke Takahashi, Haruhisa Inoue
Dopamine (DA) is a neurotransmitter in the brain, playing a central role in several disease conditions, including tetrahydrobiopterin (BH4) metabolism disorders and Parkinson's disease (PD). BH4 metabolism disorders present a variety of clinical manifestations including motor disturbance via altered DA metabolism, since BH4 is a cofactor for tyrosine hydroxylase (TH), a rate-limiting enzyme for DA synthesis. Genetically, BH4 metabolism disorders are, in an autosomal recessive pattern, caused by a variant in genes encoding enzymes for BH4 synthesis or recycling, including 6-pyruvoyltetrahydropterin synthase (PTPS) or quinonoid-dihydropteridine reductase (DHPR), respectively...
October 18, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27796756/the-transcriptional-changes-of-trim-genes-associated-with-parkinson-s-disease-on-a-model-of-human-induced-pluripotent-stem-cells
#12
V V Nenasheva, E V Novosadova, I V Makarova, O S Lebedeva, M A Grefenshtein, E L Arsenyeva, S A Antonov, I A Grivennikov, V Z Tarantul
Over the last few years, in vitro models, based on patient-derived induced pluripotent stem cells (iPSCs), have received considerable attention for modeling different neurodegenerative disorders. Using this model, we analyzed transcription of 15 tripartite motif (trim) genes in iPSCs, derived from the different groups: Parkinson's disease (PD) patients bearing mutations in different genes, patient with the sporadic form of PD, and the healthy individuals. The transcription was observed during neuronal differentiation of the cells in vitro into neuronal stem cells and terminally differentiated neurons...
October 29, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27789411/induced-pluripotent-stem-cells-ipscs-derived-from-a-symptomatic-carrier-of-a-s305i-mutation-in-the-microtubule-associated-protein-tau-mapt-gene-causing-frontotemporal-dementia
#13
Natakarn Nimsanor, Ida Jørring, Mikkel A Rasmussen, Christian Clausen, Ulrike A Mau-Holzmann, Narisorn Kitiyanant, 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 gene coding the microtubule-associated protein tau (MAPT) can cause FTDP-17 but the underlying mechanisms 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 neuronal cell type. Here, we report the generation of iPSCs from a 44-year-old symptomatic woman carrying a S305I mutation in the MAPT-gene...
October 20, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27789409/generation-of-an-isogenic-gene-corrected-ipsc-line-from-a-symptomatic-57-year-old-female-patient-with-frontotemporal-dementia-caused-by-a-p301l-mutation-in-the-microtubule-associated-protein-tau-mapt-gene
#14
Natakarn Nimsanor, Narisorn Kitiyanant, 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/27777423/characterization-and-transplantation-of-enteric-neural-crest-cells-from-human-induced-pluripotent-stem-cells
#15
W Li, L Huang, J Zeng, W Lin, K Li, J Sun, W Huang, J Chen, G Wang, Q Ke, J Duan, X Lai, R Chen, M Liu, Y Liu, T Wang, X Yang, Y Chen, H Xia, A P Xiang
The enteric nervous system (ENS) is recognized as a second brain because of its complexity and its largely autonomic control of bowel function. Recent progress in studying the interactions between the ENS and the central nervous system (CNS) has implicated alterations of the gut/brain axis as a possible mechanism in the pathophysiology of autism spectrum disorders (ASDs), Parkinson's disease (PD) and other human CNS disorders, whereas the underlying mechanisms are largely unknown because of the lack of good model systems...
October 25, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27762639/stem-cells-for-modeling-and-therapy-of-parkinson-s-disease
#16
Qingxi Zhang, Wanling Chen, Sheng Tan, Tongxiang Lin
Parkinson's disease (PD) is the second most frequent neurodegenerative disease after Alzheimer's disease, which is characterized by low level of dopamine expressing in the striatum and deteriorated dopaminergic neurons (DAn) in Substantia nigra pars compacta (SNpc). Generation of PD-derived DAn including differentiation of human embryonic stem cell (hESC), human neural stem cell (hNSC), human induced pluripotent stem cell (hiPSC) and directly reprogramming provide an ideal tool to model PD, which created the possibilities of mimicking key essential pathological processes charactering single cell changes in vitro...
October 20, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27762153/olive-polyphenols-new-promising-agents-to-combat-aging-associated-neurodegeneration
#17
Fiorella Casamenti, Massimo Stefani
Clinical trials and population studies indicate the healthy virtues of the Mediterranean diet and its main lipid component, extra-virgin olive oil (EVOO). Olive leaves and EVOO contain many phenolics effective against several aging and lifestyle-related diseases, including neurodegeneration, both in animal models and in humans. Recent research has shown that such protection stems from several effects, including (i.) the interference with the aggregation of peptides/proteins found in amyloid diseases, particularly in Alzheimer's and Parkinson's diseases; (ii...
October 20, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27760320/generating-late-onset-human-ipsc-based-disease-models-by-inducing-neuronal-age-related-phenotypes-through-telomerase-manipulation
#18
Elsa Vera, Nazario Bosco, Lorenz Studer
Modeling late-onset disorders such as Parkinson's disease (PD) using iPSC technology remains a challenge, as current differentiation protocols yield cells with the properties of fetal-stage cells. Here, we tested whether it is possible to accelerate aging in vitro to trigger late-onset disease phenotypes in an iPSC model of PD. In order to manipulate a factor that is involved in natural aging as well as in premature aging syndromes, we used telomere shortening as an age-inducing tool. We show that shortened telomeres result in age-associated as well as potentially disease-associated phenotypes in human pluripotent stem cell (hPSC)-derived midbrain dopamine (mDA) neurons...
October 18, 2016: Cell Reports
https://www.readbyqxmd.com/read/27742845/efficiently-specified-ventral-midbrain-dopamine-neurons-from-human-pluripotent-stem-cells-under-xeno-free-conditions-restore-motor-deficits-in-parkinsonian-rodents
#19
Jonathan C Niclis, Carlos W Gantner, Walaa F Alsanie, Stuart J McDougall, Chris R Bye, Andrew G Elefanty, Edouard G Stanley, John M Haynes, Colin W Pouton, Lachlan H Thompson, Clare L Parish
: : Recent studies have shown evidence for the functional integration of human pluripotent stem cell (hPSC)-derived ventral midbrain dopamine (vmDA) neurons in animal models of Parkinson's disease. Although these cells present a sustainable alternative to fetal mesencephalic grafts, a number of hurdles require attention prior to clinical translation. These include the persistent use of xenogeneic reagents and challenges associated with scalability and storage of differentiated cells. In this study, we describe the first fully defined feeder- and xenogeneic-free protocol for the generation of vmDA neurons from hPSCs and utilize two novel reporter knock-in lines (LMX1A-eGFP and PITX3-eGFP) for in-depth in vitro and in vivo tracking...
October 14, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27739432/purification-of-functional-human-es-and-ipsc-derived-midbrain-dopaminergic-progenitors-using-lrtm1
#20
Bumpei Samata, Daisuke Doi, Kaneyasu Nishimura, Tetsuhiro Kikuchi, Akira Watanabe, Yoshimasa Sakamoto, Jungo Kakuta, Yuichi Ono, Jun Takahashi
Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (mDA) neurons for cell replacement therapy for Parkinson's disease (PD). However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. To eliminate these unwanted cells, cell sorting using antibodies for specific markers such as CORIN or ALCAM has been developed, but neither marker is specific for ventral midbrain. Here we employ a double selection strategy for cells expressing both CORIN and LMX1A::GFP, and report a cell surface marker to enrich mDA progenitors, LRTM1...
October 14, 2016: Nature Communications
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