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Moreover, aberrant expression of an RBP in a disease state would have deleterious downstream effects on synaptic function. While many underlying mechanisms of synaptic dysfunction in Alzheimer's disease (AD) have been proposed, the contribution of RBPs has been relatively unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate alterations in RBP-messenger RNA (mRNA) interactions in AD, and its overall impact on the disease-related proteome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We first utilized RNA-immunoprecipitation to investigate interactions between RBP, DJ-1 (Parkinson's Disease protein 7) and target mRNAs in controls and AD. Surface Sensing of Translation \u2013 Proximity Ligation Assay (SUnSET-PLA) and western blotting additionally quantified alterations in mRNA translation and protein expression of DJ-1 targets. Finally, we utilized an unbiased bioinformatic approach that connects AD-related pathways to two RBPs, DJ-1 and FMRP (Fragile X messenger ribonucleoprotein 1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We find that oligomeric DJ-1 in AD donor synapses were less dynamic in their ability to bind and unbind mRNA compared to synapses from cognitively unimpaired, neuropathologically-verified controls. Furthermore, we find that DJ-1 associates with the mRNA coding for FMRP,\n                      <jats:italic toggle=\"yes\">Fmr1<\/jats:italic>\n                      , leading to its reduced synaptic expression in AD. Through the construction of protein-protein interaction networks, aberrant expression of DJ-1 and FMRP are predicted to lead to the upregulation of key AD-related pathways, such as thyroid hormone stimulating pathway, autophagy, and ubiquitin mediated proteolysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DJ-1 and FMRP are novel targets that may restore established neurobiological mechanisms underlying AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877241291175","type":"journal-article","created":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T03:12:18Z","timestamp":1732849938000},"page":"763-777","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["DJ-1-mediated repression of the RNA-binding protein FMRP is predicted to impact known Alzheimer's disease-related protein networks"],"prefix":"10.1177","volume":"102","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9303-8184","authenticated-orcid":false,"given":"Ayse","family":"Uneri","sequence":"first","affiliation":[{"name":"Department of Translational Neuroscience, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin J","family":"McArdle","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel H","family":"Barth","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Keene","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA"},{"name":"Department of Gerontology and Geriatric Medicine, Wake Forest Alzheimer's Disease Research Center, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Craft","sequence":"additional","affiliation":[{"name":"Department of Gerontology and Geriatric Medicine, Wake Forest Alzheimer's Disease Research Center, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6502-057X","authenticated-orcid":false,"given":"Kimberly F","family":"Raab-Graham","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA"},{"name":"Department of Gerontology and Geriatric Medicine, Wake Forest Alzheimer's Disease Research Center, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,11,29]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/bfgp\/elq028"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2673"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.54"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10577-005-0848-1"},{"key":"e_1_3_5_6_2","first-page":"2350","article-title":"Role of FMRP in rapid antidepressant effects and synapse regulation","volume":"26","author":"Heaney CF","year":"2021","unstructured":"Heaney CF, Namjoshi SV, Uneri A, et al. 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