{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T01:59:31Z","timestamp":1755223171348,"version":"3.43.0"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small Methods"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Repeat expansion of d(G<jats:sub>4<\/jats:sub>C<jats:sub>2<\/jats:sub>) in the noncoding region of the <jats:italic>C9orf72<\/jats:italic> gene contributes to neurodegenerative diseases. The repeat expansion transcript r(G<jats:sub>4<\/jats:sub>C<jats:sub>2<\/jats:sub>) induces RNA\/peptide accumulation, which, in turn, induces cytotoxicity and accelerates the development of neurodegenerative diseases. Such cytotoxic accumulation is triggered by peptide aggregation. Here, a technique is developed to prevent accumulation by regulating RNA interactions, assuming that RNA structure is important for peptide interactions. A screening method is used to identify compounds that suppress RNA accumulation of r(G<jats:sub>4<\/jats:sub>C<jats:sub>2<\/jats:sub>) repeats. The four compounds are identified with wide \u03c0\u2010planes containing hydroxyl, methoxy, and cyclic ether groups that suppressed RNA accumulation. Interestingly, these compounds also suppressed RNA\/peptide accumulation in neuroblastoma cells, indicating that RNA accumulation is a key regulator of RNA\/peptide cytotoxic aggregate formation. In vitro and in silico physicochemical analyses reveal that these compounds bind to the loop region of the G\u2010quadruplex via hydrogen bonds or CH\u2010\u03c0 interactions, resulting in an altered loop conformation. Importantly, these conformational changes inhibited RNA G\u2010quadruplex associations. These results show that conformational changes are promising for controlling the interactions between G\u2010quadruplexes and further RNA accumulation. These findings may be useful in the development of therapeutic strategies for the treatment of neurodegenerative diseases.<\/jats:p>","DOI":"10.1002\/smtd.202401630","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T13:50:33Z","timestamp":1743342633000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Controlling the Local Conformation of RNA G\u2010Quadruplex Results in Reduced RNA\/Peptide Cytotoxic Accumulation Associated with <i>C9orf72<\/i> ALS\/FTD"],"prefix":"10.1002","volume":"9","author":[{"given":"Saki","family":"Matsumoto","sequence":"first","affiliation":[{"name":"Frontier Institute for Biomolecular Engineering Research (FIBER) Konan University (Japan)  7\u20101\u201020 Minatojima\u2010minamimachi Chuo\u2010ku Kobe 650\u20100047 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6161-9817","authenticated-orcid":false,"given":"Hisae","family":"Tateishi\u2010Karimata","sequence":"additional","affiliation":[{"name":"Frontier Institute for Biomolecular Engineering Research (FIBER) Konan University (Japan)  7\u20101\u201020 Minatojima\u2010minamimachi Chuo\u2010ku Kobe 650\u20100047 Japan"},{"name":"Graduate school of Frontiers of Innovative Research in Science and Technology (FIRST) Konan University (Japan)  7\u20101\u201020 Minatojima\u2010minamimachi Chuo\u2010ku Kobe 650\u20100047 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuya","family":"Ohyama","sequence":"additional","affiliation":[{"name":"Frontier Institute for Biomolecular Engineering Research (FIBER) Konan University (Japan)  7\u20101\u201020 Minatojima\u2010minamimachi Chuo\u2010ku Kobe 650\u20100047 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2928-7028","authenticated-orcid":false,"given":"Naoki","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Frontier Institute for Biomolecular Engineering Research (FIBER) Konan University (Japan)  7\u20101\u201020 Minatojima\u2010minamimachi Chuo\u2010ku Kobe 650\u20100047 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0047-2"},{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1872189"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.10.003"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4272"},{"key":"e_1_2_8_2_3","first-page":"10","author":"Freibaum B. 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