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Fruzsina Hobor, Andre Dallmann, Neil J Ball, Carla Cicchini, Cecilia Battistelli, Roksana W Ogrodowicz, Evangelos Christodoulou, Stephen R Martin, Alfredo Castello, Marco Tripodi, Ian A Taylor, Andres Ramos
Exosomal miRNA transfer is a mechanism for cell-cell communication that is important in the immune response, in the functioning of the nervous system and in cancer. Syncrip/hnRNPQ is a highly conserved RNA-binding protein that mediates the exosomal partition of a set of miRNAs. Here, we report that Syncrip's amino-terminal domain, which was previously thought to mediate protein-protein interactions, is a cryptic, conserved and sequence-specific RNA-binding domain, designated NURR (N-terminal unit for RNA recognition)...
February 26, 2018: Nature Communications
Shireen A Hedya, Marwa M Safar, Ashraf K Bahgat
Nuclear receptor related 1 (Nurr1) orphan receptor has emerged as a promising contender in ameliorating Parkinson's disease; thus, finding a suitable activator of Nurr1 receptor is an attracting target for treating PD. Cilostazol, a phosphodiesterase-3 inhibitor, recently showed a favorable neuroprotective activity in multiple devastating central disorders, yet the possible antiparkinsonian activity of the drug has not been fully elucidated. Thus, the aim of this study is to explore the neuroprotective effect of cilostazol in rotenone-induced PD model in rats...
February 10, 2018: Molecular Neurobiology
Devin E Prior, Emily Nurre, Stephanie L Roller, David Kline, Ramit Panara, Amro M Stino, John A Davis, Miriam L Freimer, W David Arnold
INTRODUCTION: This study aimed to identify infections in patients with myasthenia gravis, dermatomyositis, and chronic inflammatory demyelinating polyradiculoneuropathy, and to investigate the relationship between infection and immunomodulation. METHODS: A retrospective chart review examined 631 patients with myasthenia gravis (n = 358), chronic inflammatory demyelinating polyradiculoneuropathy (n = 124), and dermatomyositis (n = 149) patients over a 10-year time period...
December 6, 2017: Muscle & Nerve
Simin Jamali, Hossein Mostafavi, Ghasem Barati, Mehdi Eskandari, Samad Nadri
Parkinson's disease (PD) is a neurodegenerative disorder of the brain which is produced by the damage to dopaminergic neurons. Stem cell transplantation with a nanofibrous scaffold is one of the encouraging strategies for Parkinson's disease therapy. In this study, human mesenchymal stem cells (MSCs) from eye trabecular meshwork (TM) were differentiated into dopaminergic neurons on nanofibrous scaffold. After Trabecular meshwork biopsy, MSCs were isolated, cultivated on Poly-l-Lactide Acid (PLLA) nanofibrous scaffold (fabricated by electrospinning methods) and treated with medium containing DMEM supplemented with RA, IBMX and forskolin for 7 days...
November 2017: Biologicals: Journal of the International Association of Biological Standardization
J A Jaffey, P Nurre, A B Cannon, A E DeClue
BACKGROUND: Clinicians alter dosing for desoxycorticosterone pivalate (DOCP) to mitigate costs, but this practice has not been critically evaluated in a prospective clinical trial. HYPOTHESIS/OBJECTIVES: The duration of action of DOCP is longer than 30 days in dogs with primary hypoadrenocorticism (PH). ANIMALS: A total of 53 client-owned dogs with PH. Twenty-four dogs with newly diagnosed PH (Group 1) and 29 dogs with treated PH (Group 2)...
November 2017: Journal of Veterinary Internal Medicine
Sudha Saryu Malhotra, Satish Kumar Gupta
Nur-77, a member of the NR4A sub-family of nuclear orphan receptors, is downregulated in the placentae of pre-eclamptic women. Here, we investigate the relevance of Nor-1, Nurr-1 and Nur-77 in trophoblastic cell differentiation. Their transcript levels were found to be significantly upregulated in BeWo cells treated with forskolin. The maximum increase was observed after 2 h, with a second peak in the expression levels after 48 h. The expression of NR4A sub-family members was also found to be upregulated in BeWo cells after treatment with hCG and GnRH...
2017: Cellular & Molecular Biology Letters
Susan M Corley, Shan-Yuan Tsai, Marc R Wilkins, Cynthia Shannon Weickert
Many genes are differentially expressed in the cortex of people with schizophrenia, implicating factors that control transcription more generally. Hormone nuclear receptors dimerize to coordinate context-dependent changes in gene expression. We hypothesized that members of two families of nuclear receptors (NR4As), and retinoid receptors (RARs and RXRs), are altered in the dorsal lateral prefrontal cortex (DLPFC) of people with schizophrenia. We used next generation sequencing and then qPCR analysis to test for changes in mRNA levels for transcripts encoding nuclear receptors: orphan nuclear receptors (3 in the NR4A, 3 in the RAR, 3 in the RXR families and KLF4) in total RNA extracted from the DLPFC from people with schizophrenia compared to controls (n = 74)...
2016: PloS One
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...
March 15, 2017: ACS Chemical Neuroscience
Subramanian Mariappan, Wieslaw Bogdanowicz, Hanumanthan Raghuram, Ganapathy Marimuthu, Koilmani Emmanuvel Rajan
We conducted a set of playback experiments aimed at understanding whether distress-call structure in the greater short-nosed fruit bat Cynopterus sphinx is specific in encoding information relating to stress that attracts conspecifics. We tested the specificity by playing their distress call and its modified version at a foraging site for free-ranging bats, as well as under captive conditions involving either a small group or individuals. In a separate playback experiment, bats showed a significantly greater response when the natural call as opposed to a modified call was played back to captive as well as free-ranging bats at the foraging site...
January 2016: Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology
Yafeng Yang, Teng Ma, Jun Ge, Xin Quan, Le Yang, Shu Zhu, Liangliang Huang, Zhongyang Liu, Liang Liu, Dan Geng, Jinghui Huang, Zhuojing Luo
Neuron-like cells derived from adipose tissue-derived stem cells (ADSCs) have been considered one of the most promising cells for the treatment of neurodegenerative diseases and neurotrauma in the central nervous system (CNS). Thus far, extensive efforts have been made to facilitate neuronal differentiation of ADSCs, but limited progress has been achieved. In the present study, we tested the possibility of using a combination of electrical stimulation (ES) with Nurr-1 gene transduction to promote neuronal differentiation of ADSCs...
2016: Cell Transplantation
Pierre Leblanc, Minho Moon, Woori Kim, Inhye Jeong, Chun-Hyung Kim, Kwang-Soo Kim
The nuclear receptor subfamily 4 (NR4A) is composed of 3 related proteins sharing a DNA binding domain (DBD) and a ligand-binding domain (LBD). The nuclear receptor related 1 protein (Nurr1 or NR4A2) plays a key role in the maintenance of the dopaminergic system. Dopamine dysfunctions associated with the Nurr1 gene include Parkinson's disease, schizophrenia and manic depression among others. Furthermore, recent evidence indicates that Nurr1 is also expressed in other brain areas such as the hippocampus and plays critical roles for learning and memory...
2015: Journal of Visualized Experiments: JoVE
Madhumita Patel, Hyo Jung Moon, Bo Kyung Jung, Byeongmoon Jeong
Neuronal differentiation of tonsil-derived mesenchymal stem cells (TMSCs) is investigated in a 3D hybrid system. The hybrid system is prepared by increasing the temperature of poly(ethylene glycol)-poly(l-alanine) aqueous solution to 37 °C through the heat-induced sol-to-gel transition, in which TMSCs and growth factor releasing microspheres are suspended. The in situ formed gel exhibits a modulus of 800 Pa at 37 °C, similar to that of brain tissue, and it is robust enough to hold the microspheres and cells during the 3D culture of TMSCs...
July 15, 2015: Advanced Healthcare Materials
Sayinthen Vivekanantham, Savan Shah, Rizwan Dewji, Abbas Dewji, Chetan Khatri, Rele Ologunde
Neuroinflammation in Parkinson's disease [PD] is a process that occurs alongside the loss of dopaminergic neurons, and is associated with alterations to many cell types, most notably microglia. This review examines the key evidence contributing to our understanding of the role of inflammation-mediated degeneration of the dopaminergic (DA) nigrostriatal pathway in PD. It will consider the potential role inflammation plays in tissue repair within the brain, inflammation linked gene products that are associated with sporadic Parkinsonian phenotypes (alpha-synuclein, Parkin and Nurr 1), and developing anti-inflammatory drug treatments in PD...
2015: International Journal of Neuroscience
Yutaka Watanuki, Kazunori Kageyama, Shinobu Takayasu, Yasushi Matsuzaki, Yasumasa Iwasaki, Makoto Daimon
Ultraviolet B (UVB) radiation stimulates cutaneous melanin pigmentation. The melanosomal enzyme tyrosinase-related protein 1 (TRP1) is involved in the modulation of pigment production in response to this stressor. Recent molecular and biochemical analyses have revealed the presence of corticotropin-releasing factor (CRF) and urocortin 1 (Ucn1), together with their corresponding receptors, in mammalian skin. Although CRF and Ucn1 are thought to have potent effects on the skin system, their possible roles and regulations have yet to be determined fully...
November 2014: Peptides
Akram Mokhtarzadeh Khanghahi, Bahman Zeynali, Azimeh Akhlaghpoor, Azita Parvaneh Tafreshi, Kerstin Krieglstein
So far there is increasing evidence for the involvement of transforming growth factor beta TGFβ (transforming growth factor) in differentiation and maintenance of midbrain dopaminergic neurons. Considering that USSCs (unrestricted somatic stem cells) have the potentials to differentiate into neuron-like cells and even dopaminergic neurons and that no evidence available on the role of TGFβ signaling in dopaminergic differentiation of these cells, we investigated the presence of TGFβ signaling components in USSCs and their involvement on USSCs differentiation into early dopaminergic neurons...
November 7, 2014: Neuroscience Letters
Xuejun H Parsons
To date, the lack of a clinically-suitable source of engraftable human stem/progenitor cells with adequate neurogenic potential has been the major setback in developing safe and effective cell-based therapies for regenerating the damaged or lost CNS structure and circuitry in a wide range of neurological disorders. Similarly, the lack of a clinically-suitable human cardiomyocyte source with adequate myocardium regenerative potential has been the major setback in regenerating the damaged human heart. Given the limited capacity of the CNS and heart for self-repair, there is a large unmet healthcare need to develop stem cell therapies to provide optimal regeneration and reconstruction treatment options to restore normal tissues and function...
October 1, 2013: British Biotechnology Journal
Yu-Wei Lee, Ewa K Stachowiak, Barbara Birkaya, Christopher Terranova, Mariolina Capacchietti, Peter Claus, John M Aletta, Michal K Stachowiak
Nerve growth factor (NGF) is the founding member of the polypeptide neurotrophin family responsible for neuronal differentiation. To determine whether the effects of NGF rely upon novel Integrative Nuclear FGF Receptor-1 (FGFR1) Signaling (INFS) we utilized the PC12 clonal cell line, a long-standing benchmark model of sympathetic neuronal differentiation. We demonstrate that NGF increases expression of the fgfr1 gene and promotes trafficking of FGFR1 protein from cytoplasm to nucleus by inhibiting FGFR1 nuclear export...
2013: PloS One
Simon R W Stott, Emmanouil Metzakopian, Wei Lin, Klaus H Kaestner, Rene Hen, Siew-Lan Ang
The maintained expression of transcription factors throughout the development of mesodiencephalic dopaminergic (mDA) neurons suggests multiple roles at various stages in development. Two members of the forkhead/winged helix transcription factor family, Foxa1 and Foxa2, have been recently shown to have an important influence in the early development of mDA neurons. Here we present data demonstrating that these genes are also involved in the later maintenance of the mDA system. We conditionally removed both genes in postmitotic mDA neurons using the dopamine transporter-cre mouse...
May 1, 2013: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Yutaka Watanuki, Shinobu Takayasu, Kazunori Kageyama, Yasumasa Iwasaki, Satoru Sakihara, Ken Terui, Takeshi Nigawara, Toshihiro Suda
Recent molecular and biochemical analyses have revealed the presence of corticotropin-releasing factor (CRF) and urocortin (Ucn), together with their corresponding receptors in mammalian skin. The melanosomal enzyme tyrosinase-related protein 1 (TRP1) is involved in modulation of pigment production in response to stressors. Although CRF and Ucn are thought to have potent effects on the skin system, their possible roles and regulation have yet to be fully determined. This study aimed to explore the effects of CRF and Ucn on TRP1 gene expression using human melanoma HMV-II cells...
May 6, 2013: Molecular and Cellular Endocrinology
Kalina Duszka, Juliane G Bogner-Strauss, Hubert Hackl, Dietmar Rieder, Claudia Neuhold, Andreas Prokesch, Zlatko Trajanoski, Anne-M Krogsdam
Expression of the nuclear receptor gene, Nur77 (Nr4a1), is induced in white adipose tissue (WAT) in response to β-adrenergic stimulation and fasting. Recently, Nur77 has been shown to play a gene regulatory role in the fasting response of several other major metabolic tissues. Here we investigated the effects of Nur77 on the WAT transcriptome after fasting. For this purpose, we performed gene expression profiling of WAT from wild-type and Nur77(-/-) mice submitted to prolonged fasting. Results revealed Nur77-dependent changes in expression profiles of 135 transcripts, many involved in insulin signaling, lipid and fatty acid metabolism, and glucose metabolism...
January 2013: Molecular Endocrinology
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