{"created":"2025-06-12T01:06:43.752383+00:00","id":2000346,"links":{},"metadata":{"_buckets":{"deposit":"ebbed71c-cd64-4652-be12-75e5b7c588f0"},"_deposit":{"created_by":20,"id":"2000346","owner":"20","owners":[20],"pid":{"revision_id":0,"type":"depid","value":"2000346"},"status":"published"},"_oai":{"id":"oai:muroran-it.repo.nii.ac.jp:02000346","sets":["41:227"]},"author_link":[],"item_1716854901627":{"attribute_name":"日付","attribute_value_mlt":[{"subitem_date_issued_datetime":"2026-03-01","subitem_date_issued_type":"Available"}]},"item_81_date_granted_17":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2025-03-24"}]},"item_81_degree_grantor_10":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"室蘭工業大学"},{"subitem_degreegrantor_language":"en","subitem_degreegrantor_name":"Muroran Institute of Technology"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"10103","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_81_degree_name_11":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（工学）","subitem_degreename_language":"ja"}]},"item_81_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"アルツハイマー病（AD）は、進行性の認知機能障害や行動障害を特徴とする中枢神経系の\n変性疾患である。AD は認知症患者の60〜70%を占める最も一般的な認知症のタイプである。\nAD の主な病理学的特徴は、脳内にアミロイドβ（Aβ）を含む細胞外プラークが蓄積するこ\nとである。Aβ を標的とした免疫療法薬には大きな進展が見られており、米国食品医薬品局\n（FDA）はLeqembi™（レカネマブ）およびKisunla™（ドナネマブ）を承認した。これらの薬\nは臨床応用で一定の成果を上げているものの、AD を完全に治癒することは依然として困難\nであり、さまざまな副作用を伴う。\n近年、世界中の研究者たちによりAβ 凝集阻害剤のスクリーニングが著しく進展し、天然\n抽出物が強力なAβ 凝集阻害活性を示すケースが増えている。そのため、これらの天然抽出\n物を日常の食事に取り入れることは、AD の予防に向けた安全な手段を提供する可能性があ\nる。\n本研究では、強力なAβ 凝集阻害剤をスクリーニングするために、200 種類以上のキノコ\n類からなるライブラリを選んだ。キノコエキスをスクリーニングするために、量子ドットイ\nメージングを用いた自動化微量ハイスループットスクリーニング（MSHTS）システムを使用\nした。210 種類のキノコ抽出物のうち、11 種類がAβ 凝集阻害活性を示した。その中で、コ\nフキサルノコシカケとカバノアナタケがより優れた阻害活性を示した。\n次に、MSHTS 結果に基づいて、コフキサルノコシカケのメタノール抽出物の分画を行った。\n最初に、極性および非極性溶媒を用いてメタノール抽出物を分画した。エーテルおよび酢酸\nエチル画分がAβ 凝集阻害活性を示した。酢酸エチル画分はシリカゲルカラムクロマトグ\nラフィーを用いてさらに分画され、MSHTS アッセイにより評価した。最終的に、EC50 が2.30\n± 0.859 μg/ml の阻害活性を有する活性画分を得ることができた。しかし、さらなる分画\nに伴い活性が低下したため、未解明の複数の化合物による相乗効果があるのかもしれない。\n将来、この阻害活性のメカニズムを解明したいと考えている。\nまた、MSHTS システムを使用していくつかの変形菌類のAβ 凝集阻害活性を評価したとこ\nろ、モジホコリが高い活性を示した。さらに、50 種類のカビ類のAβ 凝集阻害活性を評価\nし、そのうち18 種類が活性を示した。\n全体として、本研究は、真核微生物がAD 予防において潜在的な価値を持つことを示唆して\nいる。MSHTS システムはハイスループットスクリーニングにおいてその可能性を示し、キノ\nコ類、変形菌類、カビ類からの潜在的な活性化合物の評価を可能にした。真核微生物をAD\n研究に取り入れることで、革新的な治療法や機能性食品の探索に新たな道が開かれ、神経変\n性疾患が引き起こす課題の解決に役立つ可能性がある","subitem_description_language":"ja","subitem_description_type":"Abstract"},{"subitem_description":"Alzheimer’s disease (AD) is a degenerative disease of the central nervous system\ncharacterized by progressive cognitive dysfunction and behavioral disorders. AD is\nthe most common type of dementia, accounting for 60–70% of dementia cases. The\nmain pathological feature of AD is the accumulation of extracellular plaques\ncontaining amyloid β (Aβ) in the brain. Significant progress has been made in\nimmunotherapeutic drugs targeting Aβ. The U.S. Food and Drug Administration (FDA)\nhas approved Leqembi™ (lecanemab-irmb) and Kisunla™ (donanemab-azbt). Although\nthese drugs have achieved certain results in clinical applications, they are still\nunable to effectively cure AD and are associated with various side effects.\nIn recent years, significant progress has been made by researchers worldwide in\nscreening for Aβ aggregation inhibitors, with natural extracts showing\nincreasingly potent Aβ aggregation inhibitory activity. Therefore, incorporating\nthese natural extracts into daily diets may offer a safe approach for the prevention\nof AD.\nIn this study, I chose a library of mushrooms (over 200) to screen potent Aβ\naggregation inhibitors. To screen mushroom extracts, I used quantum dot imaging\nbased automated microliter-scale high throughput screening (MSHTS) system. Out of\n210 mushroom extracts, 11 extracts showed Aβ aggregation inhibition. Among them\nGanoderma applanatum and Fuscoporia obliqua showed better inhibition activity. I\nwent ahead to perform MSHTS assay guided fractionation of methanol extract\nGanoderma applanatum (200 grams). Initially, methanol extract was fractionated\nusing polar and non-polar solvents. Ether and ethyl acetate fractions displayed\nAβ aggregation inhibitory activity. The ethyl acetate fraction was subjected to\nsub fractionation using silica gel column chromatography followed by MSHTS assay.\nFinally, I was able to get active fraction with inhibitory activity and EC50 is\n2.30 ± 0.859 μg/ml. However, the activity decreased with further purification,\nso there may be a synergistic effect of multiple compounds that has not yet been\nelucidated. In future, I would like to elucidate the mechanism behind its\ninhibitory activity.\nI also evaluated the Aβ aggregation inhibitory activity of some myxomycetes using\nthe MSHTS system, among which Physarum showed high activity. Furthermore, I\nevaluated the Aβ aggregation inhibitory activities of 50 molds, of which 18 showed\nactivities.\nOverall, this study indicates that eukaryotic microorganisms hold potential value\nin the prevention of AD. The MSHTS system demonstrated its prospects in highthroughput\nscreening, enabling the evaluation of potential active compounds from\nmushrooms, myxomycetes, and molds. Incorporating eukaryotic microorganisms into AD\nresearch opens new avenues for exploring innovative therapies and functional foods,\nwhich may help address the challenges posed by neurodegenerative diseases.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_81_dissertation_number_13":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第550号"}]},"item_81_text_12":{"attribute_name":"学位の種別","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"課程博士"}]},"item_81_text_14":{"attribute_name":"報告番号","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"甲第550号"}]},"item_81_text_15":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"博甲第550号"}]},"item_81_text_16":{"attribute_name":"研究科・専攻","attribute_value_mlt":[{"subitem_text_language":"ja","subitem_text_value":"工学研究科"}]},"item_81_version_type_24":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"embargoed access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_f1cf"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNames":[{"affiliationName":"室蘭工業大学","affiliationNameLang":"ja"},{"affiliationName":"Muroran Institute of Technology","affiliationNameLang":"en"}]}],"creatorNames":[{"creatorName":"Gegentuya","creatorNameLang":"en"}],"familyNames":[{"familyName":"Gegentuya","familyNameLang":"en"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2026-03-01"}],"filename":"A550.pdf","filesize":[{"value":"3.8 MB"}],"format":"application/pdf","url":{"objectType":"fulltext","url":"https://muroran-it.repo.nii.ac.jp/record/2000346/files/A550.pdf"},"version_id":"20ed5dfe-a955-42ba-a924-e0b499f28137"},{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2025-06-12"}],"filename":"A550_summary.pdf","filesize":[{"value":"134 KB"}],"format":"application/pdf","url":{"objectType":"abstract","url":"https://muroran-it.repo.nii.ac.jp/record/2000346/files/A550_summary.pdf"},"version_id":"e0e990bc-88f3-4806-a2bd-739f00bb0956"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Screening of an extract with higher amyloid β aggregation inhibitory activity from eukaryotic microorganisms and the reduction of extracellular amyloid β aggregation by the extract","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Screening of an extract with higher amyloid β aggregation inhibitory activity from eukaryotic microorganisms and the reduction of extracellular amyloid β aggregation by the extract","subitem_title_language":"en"},{"subitem_title":"真核微生物からのアミロイドβ凝集阻害活性の高い抽出物のスクリ ーニングと抽出物による細胞外アミロイドβ凝集の減少","subitem_title_language":"ja"}]},"item_type_id":"81","owner":"20","path":["227"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2025-06-12"},"publish_date":"2025-06-12","publish_status":"0","recid":"2000346","relation_version_is_last":true,"title":["Screening of an extract with higher amyloid β aggregation inhibitory activity from eukaryotic microorganisms and the reduction of extracellular amyloid β aggregation by the extract"],"weko_creator_id":"20","weko_shared_id":-1},"updated":"2025-06-12T01:15:45.550611+00:00"}