{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:47:17Z","timestamp":1787168837310,"version":"build-2736575974"},"reference-count":74,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T00:00:00Z","timestamp":1755993600000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR002529"],"award-info":[{"award-number":["UL1TR002529"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30CA082709"],"award-info":[{"award-number":["P30CA082709"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Small non\u2010coding microRNAs (miRNAs) play essential roles in Alzheimer's disease (AD) pathogenesis. Repressor element 1\u2010silencing transcription factor (REST) is involved in AD, though its regulation remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We performed real\u2010time quantitative polymerase chain reaction (qPCR) in autopsied brain tissues to determine miR\u2010153\u20103p and AD associations. A reporter\u2010based assay measured the activity of REST mRNA 3\u2032\u2010untranslated region (3\u2032\u2010UTR). Induced pluripotent stem cells (iPSC)\u2010derived neurons and human cell lines were applied to determine miR\u2010153\u20103p regulation of endogenous proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Elevation of miR\u2010153\u20103p is associated with a reduced probability of AD, while elevated REST is associated with a greater probability of AD. The 3\u2032\u2010UTR functional assay pinpointed the miR\u2010153\u20103p binding sites. miR\u2010153\u20103p treatment reduced REST, amyloid precursor protein (APP), and \u03b1\u2010synuclein (SNCA) 3\u2032\u2010UTR activities and protein levels. miR\u2010153\u20103p treatment altered REST and neuronal differentiation in iPSC\u2010derived neuronal stem cells. RNA\u2010sequencing and proteomics revealed miR\u2010153\u20103p\u2010associated networks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>miR\u2010153\u20103p reduces REST, APP, and SNCA expression, pointing toward its therapeutic and biomarker potential in neurodegenerative diseases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>With the increased emphasis on comorbidities of Alzheimer's disease (AD) and other neurodegenerative diseases, we identified that miR\u2010153\u20103p, as a master regulator, reduced a group of neurodegeneration related proteins: REST, amyloid precursor protein (APP) and \u03b1\u2010synuclein (SNCA) levels.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The elevation of miR\u2010153\u20103p levels is associated with reduced probability of AD in posterior cingulate cortex (PCC), while REST, by contrast, is associated with a greater probability of AD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>miR\u2010153\u20103p treatment alters REST protein levels and neuronal differentiation in induced pluripotent stem cells (iPSC) derived neuronal cells.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>RNA sequencing proteomics and interactome analysis revealed the role of miR\u2010153\u20103p in axonal guidance.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n           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