1 40 1 Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. URL Address <a href="http://doi.org/10.1016/j.nbd.2013.07.001" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.nbd.2013.07.001</a> Rights Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s). Pages 26-37 Volume 59 Search for Full-text Locate full-text within NEOMED Library's e-journal collections <p>Users with a NEOMED Library login can search for full-text journal articles at the following url: <a href="https://libraryguides.neomed.edu/home">https://libraryguides.neomed.edu/home</a></p> Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Proximal inhibition of p38 MAPK stress signaling prevents distal axonopathy Publisher An entity responsible for making the resource available Neurobiology of Disease Date A point or period of time associated with an event in the lifecycle of the resource 2013 2013-11 Subject The topic of the resource Glaucoma; Neurodegeneration; Neurosciences & Neurology; death; amyotrophic-lateral-sclerosis; mouse model; ocular hypertension; activated protein-kinase; up-regulation; alzheimers-disease brain; Axonopathy; experimental glaucoma; ganglion-cell neurons; Heat shock protein; p38 MAPK; rat retina; Retinal ganglion cell Creator An entity primarily responsible for making the resource Dapper J D; Crish S D; Pang I H; Calkins D J Description An account of the resource The p38 mitogen-activated protein kinase (MAPK) isoforms are phosphorylated by a variety of stress stimuli in neurodegenerative disease and act as upstream activators of myriad pathogenic processes. Thus, p38 MAPK inhibitors are of growing interest as possible therapeutic interventions. Axonal dysfunction is an early component of most neurodegenerative disorders, including the most prevalent optic neuropathy, glaucoma. Sensitivity to intraocular pressure at an early stage disrupts anterograde transport along retinal ganglion cell (RGC) axons to projection targets in the brain with subsequent degeneration of the axons themselves; RGC body loss is much later. Here we show that elevated ocular pressure in rats increases p38 MAPK activation in retina, especially in RGC bodies. Topical eye-drop application of a potent and selective inhibitor of the p38 MAPK catalytic domain (Ro3206145) prevented both the degradation of anterograde transport to the brain and degeneration of axons in the optic nerve. Ro3206145 reduced in the retina phosphorylation of tau and heat-shock protein 27, both down-stream targets of p38 IVIAPK activation implicated in glaucoma, as well as expression of two inflammatory responses. We also observed increased p38 MAPK activation in mouse models. Thus, inhibition of p38 MAPK signaling in the retina may represent a therapeutic target for preventing early pathogenesis in optic neuropathies. (C) 2013 Elsevier Inc. All rights reserved. Identifier An unambiguous reference to the resource within a given context <a href="http://doi.org/10.1016/j.nbd.2013.07.001" target="_blank" rel="noreferrer noopener">10.1016/j.nbd.2013.07.001</a> Format The file format, physical medium, or dimensions of the resource Journal Article or Conference Abstract Publication 2013 activated protein-kinase alzheimers-disease brain amyotrophic-lateral-sclerosis Axonopathy Calkins D J Crish S D Dapper J D Death Department of Pharmaceutical Sciences experimental glaucoma ganglion-cell neurons Glaucoma Heat shock protein Journal Article or Conference Abstract Publication Mouse model NEOMED College of Pharmacy Neurobiology of disease Neurodegeneration Neurosciences & Neurology Ocular Hypertension p38 MAPK Pang I H rat retina Retinal ganglion cell Up-Regulation