{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T17:05:17Z","timestamp":1782493517608,"version":"3.54.5"},"reference-count":128,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T00:00:00Z","timestamp":1628640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is an age-associated neurodegenerative disorder characterized by progressive impairment of memory, thinking, behavior, and dementia. Based on ample evidence showing neurotoxicity of amyloid-\u03b2 (A\u03b2) aggregates in AD, proteolytically derived from amyloid precursor protein (APP), it has been assumed that misfolding of A\u03b2 plays a crucial role in the AD pathogenesis. Additionally, extra copies of the <jats:italic>APP<\/jats:italic> gene caused by chromosomal duplication in patients with Down syndrome can promote AD pathogenesis, indicating the pathological involvement of the <jats:italic>APP<\/jats:italic> gene dose in AD. Furthermore, increased <jats:italic>APP<\/jats:italic> expression due to locus duplication and promoter mutation of <jats:italic>APP<\/jats:italic> has been found in familial AD. Given this background, we aimed to summarize the mechanism underlying the upregulation of <jats:italic>APP<\/jats:italic> expression levels from a cutting-edge perspective. We first reviewed the literature relevant to this issue, specifically focusing on the transcriptional regulation of <jats:italic>APP<\/jats:italic> by transcription factors that bind to the promoter\/enhancer regions. <jats:italic>APP<\/jats:italic> expression is also regulated by growth factors, cytokines, and hormone, such as androgen. We further evaluated the possible involvement of post-transcriptional regulators of <jats:italic>APP<\/jats:italic> in AD pathogenesis, such as RNA splicing factors. Indeed, alternative splicing isoforms of <jats:italic>APP<\/jats:italic> are proposed to be involved in the increased production of A\u03b2. Moreover, non-coding RNAs, including microRNAs, post-transcriptionally regulate the <jats:italic>APP<\/jats:italic> expression. Collectively, elucidation of the novel mechanisms underlying the upregulation of <jats:italic>APP<\/jats:italic> would lead to the development of clinical diagnosis and treatment of AD.<\/jats:p>","DOI":"10.3389\/fragi.2021.721579","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T09:00:45Z","timestamp":1628672445000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Transcriptional and Post-Transcriptional Regulations of Amyloid-\u03b2 Precursor Protein (APP) mRNA"],"prefix":"10.3389","volume":"2","author":[{"given":"Kaoru","family":"Sato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken-ichi","family":"Takayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,11]]},"reference":[{"key":"B1","first-page":"3444","article-title":"The Rck\/p54 Candidate Proto-Oncogene Product Is a 54-kilodalton D-E-A-D Box Protein Differentially Expressed in Human and Mouse Tissues","volume":"55","author":"Akao","year":"1995","journal-title":"Cancer Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1038\/nrm2938","article-title":"Heat Shock Factors: Integrators of Cell Stress, Development and Lifespan","volume":"11","author":"\u00c5kerfelt","year":"2010","journal-title":"Nat. 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