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https://www.readbyqxmd.com/read/28511006/novel-focused-ultrasound-gene-therapy-approach-noninvasively-restores-dopaminergic-neuron-function-in-a-rat-parkinson-s-disease-model
#1
Brian P Mead, Namho Kim, G Wilson Miller, David Hodges, Panagiotis Mastorakos, Alexander L Klibanov, James W Mandell, Jay Hirsh, Jung Soo Suk, Justin Hanes, Richard J Price
Therapies capable of decelerating, or perhaps even halting, neurodegeneration in Parkinson's disease (PD) remain elusive. Clinical trials of PD gene therapy testing the delivery of neurotrophic factors, such as the glial cell-line derived neurotrophic factor (GDNF), have been largely ineffective due to poor vector distribution throughout the diseased regions in the brain. In addition, current delivery strategies involve invasive procedures that obviate the inclusion of early stage patients who are most likely to benefit from GDNF-based gene therapy...
May 18, 2017: Nano Letters
https://www.readbyqxmd.com/read/28506996/ret-mediated-glial-cell-line-derived-neurotrophic-factor-signaling-inhibits-mouse-prostate-development
#2
Hyun-Jung Park, Eric C Bolton
In humans and rodents, the prostate gland develops from the embryonic urogenital sinus (UGS). The androgen receptor (AR) is thought to control the expression of morphogenetic genes in inductive UGS mesenchyme, which promotes proliferation and cytodifferentiation of the prostatic epithelium. However, the nature of the AR-regulated morphogenetic genes and the mechanisms whereby AR controls prostate development are not understood. Glial cell line-derived neurotrophic factor (GDNF) binds GDNF family receptor-α1 (GFRα1) and signals through activation of RET tyrosine kinase...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28499803/establishment-and-characterization-of-primary-astrocyte-culture-from-adult-mouse-brain
#3
Xiu Sun, Xin Hu, Dan Wang, Yimin Yuan, Shangyao Qin, Zijian Tan, Yakun Gu, Xiao Huang, Cheng He, Zhida Su
As a major class of glial cells, astrocytes have been indicated to play multi-roles in physiological and pathological brain. Astrocyte cultures derived from postnatal mouse brains have been extensively used to characterize their biological properties. However, the inability to culture adult mouse primary astrocytes has long stymied studies of function in adult brain. Here, we developed a protocol to successfully establish highly enriched astrocyte cultures from the brains of adult mouse. Cortical tissues were collected to prepare cell suspension by enzymatic digestion and mechanical dissociation, and then plated onto vessels pre-coated with gelatin and matrigel and cultured in DMEM medium containing 20% fetal bovine serum (FBS)...
May 10, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28493093/insights-from-mathematical-modeling-for-convection-enhanced-intraputamenal-delivery-of-gdnf
#4
Elena Belova, Christopher L Shaffer, Patrick E Trapa
Glial cell line-derived neurotrophic factor (GDNF) is a potential therapy for Parkinson's disease (PD) promoting survival and functional recovery of dopaminergic neurons when delivered to the degenerated striatum. To study the aspects of intraputamenal delivery of GDNF, a mathematical model of recombinant methionyl human GDNF (r-metHuGDNF) convection in the human putamen has been developed. The convection-enhanced delivery infusions of r-metHuGDNF were simulated at rates up to 5 μL/min. The high-rate infusions (≥1 μL/min) permit rapid and uniform distribution of drug with up to 75% of the distribution volume having a concentration within 5% of the infusate concentration...
May 11, 2017: Medical & Biological Engineering & Computing
https://www.readbyqxmd.com/read/28490528/combining-new-tools-to-assess-renal-function-and-morphology-a-holistic-approach-to-study-the-effects-of-aging-and-a-congenital-nephron-deficit
#5
Stefania Geraci, Jorge Chacón-Caldera, Luise Anne Cullen-McEwen, Lothar R Schad, Carsten Sticht, Victor G Puelles, John F Bertram, Norbert Gretz
Recently, new methods for assessing renal function in conscious mice (transcutaneous assessment) and for counting and sizing all glomeruli in whole kidneys (MRI) were described. In the present study, these methods were used to assess renal structure and function in aging mice, and in mice born with a congenital low nephron endowment. Age-related nephron loss was analysed in adult C57BL/6 mice (10-50 weeks of age) and congenital nephron deficit was assessed in glial cell line-derived neurotrophic factor heterozygous (GDNF HET) null mutant mice...
May 10, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28490466/ret-signaling-in-prostate-cancer
#6
Kechen Ban, Shu Feng, Longjiang Shao, Michael Ittmann
Purpose: Large diameter perineural prostate cancer is associated with poor outcomes. GDNF, with its co-receptor GFRα1, binds RET and activates downstream pro-oncogenic signaling. Since both GDNF and GFRα1 are secreted by nerves, we examined the role of RET signaling in prostate cancer. <p>Experimental Design: Expression of RET, GDNF and/or GFRα1 was assessed. The impact of RET signaling on proliferation, invasion and soft agar colony formation, perineural invasion and growth in vivo was determined...
May 10, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28489907/anti-oxidative-effects-of-4-hydroxybenzyl-alcohol-in-astrocytes-confer-protective-effects-in-autocrine-and-paracrine-manners
#7
Lidan Luo, Seung-Woo Kim, Hye-Kyung Lee, Il-Doo Kim, Hahnbie Lee, Ja-Kyeong Lee
4-Hydroxybenzyl alcohol (4-HBA) is an important phenolic constituent of Gastrodia elata Blume (GEB), a traditional herbal medicine used in East Asia. Many activities have been reported to underlie the beneficial effects of 4-HBA in the brain, and in particular, its anti-inflammatory, anti-oxidative, and anti-zinc-toxic effects have been implicated in the postischemic brain. Here, the authors investigated the anti-oxidative effect of 4-HBA on astrocytes and sought to identify the underlying molecular mechanisms involved...
2017: PloS One
https://www.readbyqxmd.com/read/28484241/glial-cell-line-derived-neurotrophic-factor-protects-human-islets-from-nutrient-deprivation-and-endoplasmic-reticulum-stress-induced-apoptosis
#8
Shadab Abadpour, Sven O Göpel, Simen W Schive, Olle Korsgren, Aksel Foss, Hanne Scholz
One of the key limitations to successful human islet transplantation is loss of islets due to stress responses pre- and post-transplantation. Nutrient deprivation and ER stress have been identified as important mechanisms leading to apoptosis. Glial Cell-line Derived Neurotrophic Factor (GDNF) has recently been found to promote islet survival after isolation. However, whether GDNF could rescue human islets from nutrient deprivation and ER stress-mediated apoptosis is unknown. Herein, by mimicking those conditions in vitro, we have shown that GDNF significantly improved glucose stimulated insulin secretion, reduced apoptosis and proinsulin:insulin ratio in nutrient deprived human islets...
May 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28481001/transgenic-scs-expressing-gdnf-ires-dsred-impair-nerve-regeneration-within-acellular-nerve-allografts
#9
Xueping Ee, Ying Yan, Daniel A Hunter, Lauren Schellhardt, Shelly E Sakiyama-Elbert, Susan E Mackinnon, Matthew D Wood
Providing temporally regulated glial cell line-derived neurotrophic factor (GDNF) to injured nerve can promote robust axon regeneration. However, it is poorly understood why providing highly elevated levels of GDNF to nerve can lead to axon entrapment in the zone containing elevated GDNF. This limited understanding represents an obstacle to the translation of GDNF therapies to treat nerve injuries clinically. Here, we investigated how transgenic Schwann cells (SCs) overexpressing GDNF-IRES-DsRed impact nerve regeneration...
May 8, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28475863/gzf1-mutations-expand-the-genetic-heterogeneity-of-larsen-syndrome
#10
Nisha Patel, Hanan E Shamseldin, Nadia Sakati, Arif O Khan, Ameen Softa, Fatima M Al-Fadhli, Mais Hashem, Firdous M Abdulwahab, Tarfa Alshidi, Rana Alomar, Eman Alobeid, Salma M Wakil, Dilek Colak, Fowzan S Alkuraya
Larsen syndrome is characterized by the dislocation of large joints and other less consistent clinical findings. Heterozygous FLNB mutations account for the majority of Larsen syndrome cases, but biallelic mutations in CHST3 and B4GALT7 have been more recently described, thus confirming the existence of recessive forms of the disease. In a multiplex consanguineous Saudi family affected by severe and recurrent large joint dislocation and severe myopia, we identified a homozygous truncating variant in GZF1 through a combined autozygome and exome approach...
May 4, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28474536/comments-on-an-overview-of-protocols-for-the-neural-induction-of-dental-and-oral-stem-cells-in-vitro-article-in-tissue-engineering-part-b-heng-et-al-february-2016-doi-10-1089-ten-teb-2015-0488
#11
Orsolya Pall, Bela Varga Varga, Pierre-Yves Collart-Dutilleul, Csilla Gergely, Frédéric Cuisinier
We read with interest the review of Heng et al.(2016). The article summarizes a wide range of protocols about the in vitro neurodifferentiation of different dental and oral stem cells. Our research group is also interested in the study of neurogenic potential of dental pulp stem cells, so we were pleased to find such a detailed and comprehensive review about this topic. Unfortunately when reading carefully the article, we observed numerous errors regarding for example the quantity of the products in several protocols...
May 5, 2017: Tissue Engineering. Part B, Reviews
https://www.readbyqxmd.com/read/28474535/long-term-propagation-of-porcine-undifferentiated-spermatogonia
#12
Pengfei Zhang, Xiaoxu Chen, Yi Zheng, Jinsheng Zhu, Yuwei Qin, Yinghua Lv, Wenxian Zeng
Spermatogonial stem cells (SSCs) provide the foundation for spermatogenesis and fertility throughout the adult life of a male. Genetic manipulations of SSCs combined with germ cell transplantation present a novel approach for gene therapy and production of genetically modified animals. However, the rarity of SSCs within mammalian testes remains an impediment to related applications that require sufficient numbers of SSCs, making in vitro expansion of SSCs a prerequisite. Nevertheless, long-term culture systems of SSCs from large animals have not been established yet...
May 5, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28468283/heparin-heparan-sulphate-and-the-tgf-%C3%AE-cytokine-superfamily
#13
REVIEW
Chris C Rider, Barbara Mulloy
Of the circa 40 cytokines of the TGF-β superfamily, around a third are currently known to bind to heparin and heparan sulphate. This includes TGF-β1, TGF-β2, certain bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), as well as GDNF and two of its close homologues. Experimental studies of their heparin/HS binding sites reveal a diversity of locations around the shared cystine-knot protein fold. The activities of the TGF-β cytokines in controlling proliferation, differentiation and survival in a range of cell types are in part regulated by a number of specific, secreted BMP antagonist proteins...
April 29, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28467503/zebrafish-gdnf-and-its-co-receptor-gfr%C3%AE-1-activate-the-human-ret-receptor-and-promote-the-survival-of-dopaminergic-neurons-in-vitro
#14
Tuulia Saarenpää, Konstantin Kogan, Yulia Sidorova, Arun Kumar Mahato, Igor Tascón, Heidi Kaljunen, Liying Yu, Jukka Kallijärvi, Jaana Jurvansuu, Mart Saarma, Adrian Goldman
Glial cell line-derived neurotrophic factor (GDNF) is a ligand that activates, through co-receptor GDNF family receptor alpha-1 (GFRα1) and receptor tyrosine kinase "RET", several signaling pathways crucial in the development and sustainment of multiple neuronal populations. We decided to study whether non-mammalian orthologs of these three proteins have conserved their function: can they activate the human counterparts? Using the baculovirus expression system, we expressed and purified Danio rerio RET, and its binding partners GFRα1 and GDNF, and Drosophila melanogaster RET and two isoforms of co-receptor GDNF receptor-like...
2017: PloS One
https://www.readbyqxmd.com/read/28463804/encapsulated-cell-device-approach-for-combined-electrical-stimulation-and-neurotrophic-treatment-of-the-deaf-cochlea
#15
W S Konerding, H Janssen, P Hubka, J Tornøe, P Mistrik, L Wahlberg, T Lenarz, A Kral, V Scheper
Profound hearing impairment can be overcome by electrical stimulation (ES) of spiral ganglion neurons (SGNs) via a cochlear implant (CI). Thus, SGN survival is critical for CI efficacy. Application of glial cell line-derived neurotrophic factor (GDNF) has been shown to reduce SGN degeneration following deafness. We tested a novel method for local, continuous GDNF-delivery in combination with ES via a CI. The encapsulated cell (EC) device contained a human ARPE-19 cell-line, genetically engineered for secretion of GDNF...
April 25, 2017: Hearing Research
https://www.readbyqxmd.com/read/28456938/glioprotective-effect-of-resveratrol-an-emerging-therapeutic-role-for-oligodendroglial-cells
#16
Priscila Machado Rosa, Leo Anderson Meira Martins, Diogo Onofre Souza, André Quincozes-Santos
Resveratrol is a natural polyphenol compound highly found in red wine that displays several beneficial effects on the central nervous system (CNS), preventing or slowing the progression of a wide variety of neurological diseases. Its neuroprotective role is particularly associated to modulation of antioxidant and anti-inflammatory responses in glial cells in a mechanism dependent of heme oxygenase 1 (HO-1) signaling pathway. Oligodendrocyte progenitor cells (OPC), primarily known for giving rise to mature oligodendrocytes, have emerged as dynamic cells that are also important to maintain the CNS homeostasis...
April 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28450948/preventative-effects-of-fermented-chimonobambusa-quadrangularis-shoot-on-activated-carbon-induced-constipation
#17
Guijie Li, Xiaochuan Zou, Gang Kuang, Yanrong Ren, Chaofang Deng, Qiang Lin, Xin Zhao, Song Xu, Jia-Le Song
The present study aimed to determine the preventative effects of fermented Chimonobambusa quadrangularis shoot (FCQS) on activated carbon constipation in Kun Ming mice. FCQS has a more loose fiber tissue structure than unfermented fresh C. quadrangularis shoot (CQS), which is preferable for relieving constipation. In mice fed with FCQS for 9 days the time from consumption to their first black stool defecation (117 min) was shorter than the control group (192 min) and the CQS group (148 min); however, it was longer than the normal (85 min) and bisacodyl treatment (99 min) groups...
March 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28450050/transgenic-human-embryonic-stem-cells-overexpressing-fgf2-stimulate-neuroprotection-following-spinal-cord-ventral-root-avulsion
#18
Marta Rocha Araújo, Sergiy Kyrylenko, Aline Barroso Spejo, Mateus Vidigal Castro, Rui Seabra Ferreira Junior, Benedito Barraviera, Alexandre Leite Rodrigues Oliveira
Ventral root avulsion (VRA) triggers a strong glial reaction which contributes to neuronal loss, as well as to synaptic detachment. To overcome the degenerative effects of VRA, treatments with neurotrophic factors and stem cells have been proposed. Thus, we investigated neuroprotection elicited by human embryonic stem cells (hESC), modified to overexpress a human fibroblast growth factor 2 (FGF-2), on motoneurons subjected to VRA. Lewis rats were submitted to VRA (L4-L6) and hESC/FGF-2 were applied to the injury site using a fibrin scaffold...
April 24, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28442998/glial-cell-line-derived-neurotrophic-factor-gene-delivery-in-parkinson-s-disease-a-delicate-balance-between-neuroprotection-trophic-effects-and-unwanted-compensatory-mechanisms
#19
REVIEW
Liliane Tenenbaum, Marie Humbert-Claude
Glial cell line-derived neurotrophic factor (GDNF) and Neurturin (NRTN) bind to a receptor complex consisting of a member of the GDNF family receptor (GFR)-α and the Ret tyrosine kinase. Both factors were shown to protect nigro-striatal dopaminergic neurons and reduce motor symptoms when applied terminally in toxin-induced Parkinson's disease (PD) models. However, clinical trials based on intraputaminal GDNF protein administration or recombinant adeno-associated virus (rAAV)-mediated NRTN gene delivery have been disappointing...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28441076/a-novel-neuroprotective-small-molecule-for-glial-cell-derived-neurotrophic-factor-induction-and-photoreceptor-rescue
#20
Petr Baranov, Hong Lin, Kathryn McCabe, David Gale, Shenshen Cai, Burke Lieppman, Dwight Morrow, Phoebe Lei, Justin Liao, Michael Young
PURPOSE: Degenerative diseases of the retina, such as retinitis pigmentosa and age-related macular degeneration, are characterized by the irreversible loss of photoreceptors. Several growth factors, including glial cell derived neurotrophic factor (GDNF), have been shown to rescue retinal neurons. An alternative strategy to direct GDNF administration is its induction in host retina by small molecules. Here we studied the ability of a novel small molecule GSK812 to induce GDNF in vitro/in vivo and rescue photoreceptors...
April 25, 2017: Journal of Ocular Pharmacology and Therapeutics
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