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Nontoxic RsDPLA As a Potent Antagonist of Toxic Lipopolysaccharide
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Nilofer Qureshi, Bruce W. Jarvis, Kuni Takayama
These two complexes could interact with another transmembrane protein (this would be the signaling protein) and cause a dimerization of these proteins. We suggest that when the CD14-LPS complex associates with the signaling protein (this would constitute the third level of competitive binding), a strong signal is generated, which initiates the activation of the cell. This signaling protein could be one or more of the three classes of transmembrane receptors described by Bernard (70). We suggest that when CD14-RsDPLA associates with the signaling protein, only a weak signal is generated, which is not adequate to activate the cell. A similar mechanism was proposed by Davis et al. (71) for the activation of the ciliary neurotrophic factor receptor complex. An alternative mechanism might be proposed where CD 14 transfers the toxic LPS directly to the receptor (the signaling unit) to initiate signal transduction.
Regeneration: Nanomaterials for Tissue Regeneration
Published in Harry F. Tibbals, Medical Nanotechnology and Nanomedicine, 2017
Encapsulation of cells for neurotrophic factor delivery has been used experimentally in treatment of Huntington’s disease [134]. Huntington’s is a genetic disease with severe impacts on cognitive, psychological, and motor functions. It is associated with the progressive loss of efferent neurons of the striatum responsible for the release of the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory neurotransmitter in the vertebrate central nervous system. There is no clinical treatment to date. The development of the condition is protracted over many years after onset, and the genetic marker is known, so there is a possibility that a strategy of protecting neurons would be effective. Neurotrophic factors such as ciliary neurotrophic factor (CNTF) have been shown to protect striatal neurons in experimental animal models of Huntington’s disease [135].
Sexual Differentiation of a Neuromuscular System
Published in Akira Matsumoto, Sexual Differentiation of the Brain, 2017
Scott E. Christensen, S. Marc Breedlove, Cynthia L. Jordan
Nancy Forger23,24 has presented data to suggest that androgen spares the SNB system by regulating either the production of a neurotrophic factor or the sensitivity of the system to some such factor. Perinatal delivery of ciliary neurotrophic factor (CNTF) to the BC/LA complex spares both the muscles and their motoneurons from cell death, if only for the duration of the treatment.23 This experiment raised the possibility that androgen spares the system by inducing the release of CNTF from some tissues in the region of the target muscles. However, the finding that knockout mice lacking the gene for CNTF display a normal SNB system at birth shows that CNTF is not necessary for the sparing of the system and suggests that CNTF is not normally involved in that process. But perhaps androgen affects a CNTF-like factor, since male mice lacking the gene for the CNTF receptor α (CNTFRα) have significantly fewer SNB cells at birth, equivalent to female controls.24 Indeed, the finding that androgen treatment regulates the expression of CNTFRα in BC/LA muscles is consistent with the idea that androgen makes the muscles sensitive to CNTF-like substances and normally induces the release of a CNTF-like factor from some nearby tissues. Presumably, androgen does not act upon the SNB motoneurons themselves to produce any neurotrophic factor, because SNB motoneurons with defective copies of the androgen receptor gene are just as likely to be spared as androgen-insensitive SNB cells.22
Intraocular delivery considerations of ocular biologic products and key preclinical determinations
Published in Expert Opinion on Drug Delivery, 2023
Patrick Hughes, Hongwen M. Rivers, Vladimir Bantseev, Chun-Wan Yen, Hanns-Christian Mahler, Swati Gupta
Encapsulated cell technology (ECT) has been developed by Neurotech Pharmaceuticals, Inc. in which cells are encapsulated and packed into an intravitreal implant. The cells are engineered to express the therapeutic protein of interest at a designed rate. The system utilizes immortalized human retinal pigmented epithelial cells to express the desired protein, which diffuses from the implant into the vitreous. Initial results with an implant that expressed a soluble VEGF receptor (VEGFR) fusion protein (NT-503) were not found to be promising for nAMD [126]. The fusion protein was expressed at rates of 2 to 12 µg/day, but the system did not meet the primary endpoint in Phase 2 studies [127]. However, the company has found success with an alternative system that expresses ciliary neurotrophic factor (CNTF). The Renexus® (NT-501) intravitreal implant expressing CNTF has shown positive results in Phase 3 trials for the treatment of macular telangiectasia type 2 and, in 2019, Neurotech was granted Fast Track designation for Renexus® by the FDA for treatment of RP and macular telangiectasia [128].
Protective effects of Forsythiae fructus and Cassiae semen water extract against memory deficits through the gut-microbiome-brain axis in an Alzheimer’s disease model
Published in Pharmaceutical Biology, 2022
Da Sol Kim, Ting Zhang, Sunmin Park
The hippocampal tissues were collected from three randomly selected rats per group. Total RNA was isolated from tissues using a monophasic solution of phenol and guanidine isothiocyanate (Trizol reagent, Invitrogen, Rockville, MD, USA). cDNA was produced using a mixture of total RNA, superscript III reverse transcriptase, and high fidelity Taq DNA polymerase (1:1:1, v:v:v) by polymerase chain reaction (PCR) and mixed with the primers of genes of interest and SYBR Green mix. The expressions of genes of interest were determined using a realtime PCR machine (BioRad Laboratories, Hercules, CA, USA). The primers used for ciliary neurotrophic factor (CNTF), BDNF, TNF-α, IL-1β, and β-actin were as previously described (Peinnequin et al. 2004). Gene expression levels in samples were quantitated using the comparative cycle of threshold (CT) method (Livak and Schmittgen 2001).
Decreased Expression of Glial-Derived Neurotrophic Factor Receptors in Glaucomatous Human Retinas
Published in Current Eye Research, 2022
Abhigna Akurathi, Erin A. Boese, Randy H. Kardon, Johannes Ledolter, Markus H. Kuehn, Matthew M. Harper
In addition to the ability to lower IOP, these medications may have off-target effects. We have recently evaluated the relationship of brain-derived neurotrophic factor (BDNF) and the BDNF receptor tropomyosin receptor kinase B (TrkB), with the use of glaucoma medications and outcomes derived from patient medical histories in control and glaucomatous eyes. This study identified a relationship between BDNF expression and the use of prostaglandin analogs.4 Additionally, the expression of TrkB was correlated with the use of carbonic anhydrase inhibitors, the use of beta-blockers, and the total number of drugs used for the treatment of glaucoma. TrkB expression also correlated with the last measured intraocular pressure (IOP) from the medical records. In addition to BDNF, several other neurotrophic factors have been investigated for their ability to protect neurons from the effect of neurodegenerative disease. These include Ciliary Neurotrophic Factor (CNTF) and Glial Derived Neurotrophic Factor (GDNF).