{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T03:51:09Z","timestamp":1790135469465,"version":"4.0.1"},"reference-count":249,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,1,29]],"date-time":"2015-01-29T00:00:00Z","timestamp":1422489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K003771\/1"],"award-info":[{"award-number":["MR\/K003771\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:p>\n                    Altered\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    metabolism is a key pathophysiological component causing several neurodegenerative diseases. Genetic mutations causing neurodegeneration occur in coding and noncoding regions of seemingly unrelated genes whose products do not always contribute to the gene expression process. Several pathogenic mechanisms may coexist within a single neuronal cell, including\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    \/protein toxic gain\u2010of\u2010function and\/or protein loss\u2010of\u2010function. Genetic mutations that cause neurodegenerative disorders disrupt healthy gene expression at diverse levels, from chromatin remodelling, transcription, splicing, through to axonal transport and repeat\u2010associated non\u2010\n                    <jats:styled-content style=\"fixed-case\">ATG<\/jats:styled-content>\n                    (\n                    <jats:styled-content style=\"fixed-case\">RAN<\/jats:styled-content>\n                    ) translation. We address neurodegeneration in repeat expansion disorders [\n                    <jats:styled-content style=\"fixed-case\">H<\/jats:styled-content>\n                    untington's disease, spinocerebellar ataxias,\n                    <jats:styled-content style=\"fixed-case\">C9ORF72<\/jats:styled-content>\n                    \u2010related amyotrophic lateral sclerosis (\n                    <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content>\n                    )] and in diseases caused by deletions or point mutations (spinal muscular atrophy, most subtypes of familial\n                    <jats:styled-content style=\"fixed-case\">ALS<\/jats:styled-content>\n                    ). Some neurodegenerative disorders exhibit broad dysregulation of gene expression with the synthesis of hundreds to thousands of abnormal messenger\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    (\n                    <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                    ) molecules. However, the number and identity of aberrant\n                    <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                    s that are translated into proteins \u2013 and how these lead to neurodegeneration \u2013 remain unknown. The field of RNA biology research faces the challenge of identifying pathophysiological events of dysregulated gene expression. In conclusion, we discuss current research limitations and future directions to improve our characterization of pathological mechanisms that trigger disease onset and progression.\n                  <\/jats:p>","DOI":"10.1111\/nan.12187","type":"journal-article","created":{"date-parts":[[2014,10,16]],"date-time":"2014-10-16T03:31:54Z","timestamp":1413430314000},"page":"109-134","source":"Crossref","is-referenced-by-count":41,"title":["Invited Review: Decoding the pathophysiological mechanisms that underlie\n                    <scp>RNA<\/scp>\n                    dysregulation in neurodegenerative disorders: a review of the current state of the art"],"prefix":"10.1111","volume":"41","author":[{"given":"Matthew J.","family":"Walsh","sequence":"first","affiliation":[{"name":"Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience University of Sheffield Sheffield 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