{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:01:31Z","timestamp":1790913691072,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sapienza University and Fondazione Istituto Italiano di Tecnologia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The main goal of this review is to provide an updated overview of the involvement of the RNA-binding protein (RBP) HuD, encoded by the ELAVL4 gene, in nervous system development, maintenance, and function, and its emerging role in nervous system diseases. A particular focus is on recent studies reporting altered HuD levels, or activity, in disease models and patients. Substantial evidence suggests HuD involvement in Parkinson\u2019s disease (PD), Alzheimer\u2019s disease (AD), and amyotrophic lateral sclerosis (ALS). Interestingly, while possible disease-causing mutations in the ELAVL4 gene remain elusive, a common theme in these diseases seems to be the altered regulation of HuD at multiple steps, including post-transcriptional and post-translational levels. In turn, the changed activity of HuD can have profound implications for its target transcripts, which are overly stabilized in case of HuD gain of function (as proposed in PD and ALS) or reduced in case of decreased HuD binding (as suggested by some studies in AD). Moreover, the recent discovery that HuD is a component of pathological cytoplasmic inclusion in both familial and sporadic ALS patients might help uncover the common molecular mechanisms underlying such complex diseases. We believe that deepening our understanding of the involvement of HuD in neurodegeneration could help developing new diagnostic and therapeutic tools.<\/jats:p>","DOI":"10.3390\/ijms232314606","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T09:50:52Z","timestamp":1669197052000},"page":"14606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases"],"prefix":"10.3390","volume":"23","author":[{"given":"Beatrice","family":"Silvestri","sequence":"first","affiliation":[{"name":"Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"Center for Life Nano & Neuro-Science, Fondazione Istituto Italiano di Tecnologia (IIT), 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Mochi","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2101-4474","authenticated-orcid":false,"given":"Maria Giovanna","family":"Garone","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology, Murdoch Children\u2019s Research Institute, The Royal Children\u2019s Hospital, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9999-7223","authenticated-orcid":false,"given":"Alessandro","family":"Rosa","sequence":"additional","affiliation":[{"name":"Department of Biology and Biotechnologies \u201cCharles Darwin\u201d, Sapienza University of Rome, 00185 Rome, Italy"},{"name":"Center for Life Nano & Neuro-Science, Fondazione Istituto Italiano di Tecnologia (IIT), 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1261\/rna.039164.113","article-title":"Emerging complexity of the HuD\/ELAVl4 gene; implications for neuronal development, function, and dysfunction","volume":"19","author":"Bronicki","year":"2013","journal-title":"RNA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4197","DOI":"10.1128\/MCB.00316-10","article-title":"miR-375 inhibits differentiation of neurites by lowering HuD levels","volume":"30","author":"Abdelmohsen","year":"2010","journal-title":"Mol. 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