{"id":"hum0488","version":1,"url":"https://humandbs.dbcls.jp/research/hum0488/v1","datePublished":"2026-01-05","versions":[{"version":1,"datePublished":"2026-01-05"}],"title":{"ja":"筋萎縮性側索硬化症におけるTDP-43関連遺伝子発現制御機構の解析","en":"Analysis of Mechanisms Regulating TDP-43-Related Gene Expression in Amyotrophic Lateral Sclerosis (ALS)"},"summary":{"aims":{"ja":"筋萎縮性側索硬化症（amyotrophic lateral sclerosis：ALS）は運動神経の変性により、全身の筋力低下を起こして嚥下障害や呼吸障害を生じる致死性の神経変性疾患である。現在根本的な治療薬がなく一刻も早い新規治療法の開発が望まれている。ALSの発症原因は不明の点が多いが、大部分のALS患者の運動神経ではRNA結合蛋白質TDP-43の核から細胞質への局在変化とそこでの異常沈着がみられ、TDP-43によるRNA代謝の何らかの異常がALSの発症に関与することが示唆されている。本研究の目的はALSにおけるRNA代謝異常の意義を明らかにすることである。","en":"Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes systemic muscle weakness, dysphagia, and respiratory failure. Currently, there are no definitive cures available, and the development of new treatments is urgently needed. The causes of ALS remain largely unknown, but in most ALS patients, there is a mislocalization of the RNA-binding protein TDP-43 from the nucleus to the cytoplasm in motor neurons, along with its abnormal aggregation. This suggests that some abnormalities in RNA metabolism mediated by TDP-43 are related to the onset of ALS. This study aims to elucidate the significance of RNA metabolic abnormalities in ALS."},"methods":{"ja":"全ゲノム解析、bulk RNA-seq解析、single-nucleus RNA-seq解析、single-nucleus ATAC-seq解析","en":"WGS, bulk RNA-seq, single-nucleus RNA-seq, single-nucleus ATAC-seq"},"targets":{"ja":"大阪大学医学部附属病院および東京都健康長寿医療センターにて病理診断目的に解剖、凍結保存されたALS（TDP-43病理所見あり）13症例、ALS以外の疾患（TDP-43病理所見なし）13症例","en":"13 ALS patients whose autopsy pathology confirmed intracellular mislocalization and abnormal deposition of TDP-43 and 13 patients with other diseases who had no TDP-43 pathology (non-ALS) at Osaka University Hospital and Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology."},"url":{"ja":null,"en":null}},"listingSummary":{"methods":{"ja":"配列決定\n発現\nクロマチン構造","en":"Sequencing, expression profiling, and chromatin structure analysis"},"targets":{"ja":"ALS：13症例\n非ALS：13症例\n（日本人）","en":"ALS: 13 cases\nnon-ALS: 13 cases\n(Japanese)"},"typeOfData":{"ja":"NGS\n（WGS、bulk RNA-seq、snRNA-seq、snATAC-seq）","en":"NGS\n(WGS, bulk RNA-seq, snRNA-seq, snATAC-seq)"}},"releaseNote":{"ja":"・筋萎縮性側索硬化症（ALS）7症例および非ALS疾患7症例の凍結延髄組織から抽出したRNAを用いたbulk RNA-seq解析の結果をfastqファイルにて提供する。\n・ALS6症例および非ALS疾患6症例の凍結大脳組織および脊髄組織より採取した核より抽出したRNA/DNAを対象としたsnRNA-seq解析、および、snATAC-seq解析、ならびに凍結組織より抽出したDNAを用いたWGS解析の結果をfastqファイルにて提供する。","en":"- RNA extracted from frozen medulla oblongata tissues of 7 patients with amyotrophic lateral sclerosis (ALS) and 7 patients with non-ALS diseases were used for bulk RNA-seq analysis. Fastq files are provided.\n- DNA/RNA extracted from nuclei obtained from frozen brain and spinal cord tissues of 6 patients with ALS and 6 patients with non-ALS diseases were used for snRNA-seq and snATAC-seq analyses. DNA extracted from frozen tissues of these subjects were used for WGS analysis. Fastq files are provided."},"dataProviders":[{"name":{"ja":"長野 清一","en":"Seiichi Nagano"},"organization":{"name":{"ja":"大阪大学大学院医学系研究科 神経難病認知症探索治療学","en":"Department of Neurotherapeutics, Osaka University Graduate School of Medicine"}}}],"researchProjects":[],"grants":[{"title":{"ja":"神経軸索内局所翻訳機構に着目したALS/FTLDの病態解明と治療法開発","en":"Elucidation of the pathogenesis and development of the treatment strategy of ALS/FTLD focusing on the local translation in neuronal axons"},"agency":{"ja":"科学研究費助成事業 基盤研究（B）","en":"KAKENHI Grant-in-Aid for Scientific Research (B)"},"grantIds":["21H02841"]},{"title":{"ja":"神経細胞内鉄代謝障害に基づく筋萎縮性側索硬化症の病態解明","en":"Elucidation of the pathogenesis of amyotrophic lateral sclerosis based on neuronal iron metabolism disorders"},"agency":{"ja":"科学研究費助成事業 新学術領域研究（研究領域提案型）","en":"KAKENHI Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)"},"grantIds":["22H04811"]},{"title":{"ja":"細胞種特異的スプライシング変化を介したALS発症機序の解明","en":"Elucidation of the mechanism of ALS onset via cell type-specific splicing alterations"},"agency":{"ja":"科学研究費助成事業 挑戦的研究（萌芽）","en":"KAKENHI Grant-in-Aid for Challenging Research (Exploratory)"},"grantIds":["23K18265"]},{"title":{"ja":"患者組織由来RNA-seqの統合的解析によるALS病態関連因子の同定","en":"Identification of ALS pathology-related factors through integrated analysis of patient tissue-derived RNA-seq data"},"agency":{"ja":"科学研究費助成事業 基盤研究（B）","en":"KAKENHI Grant-in-Aid for Scientific Research (B)"},"grantIds":["24K02370"]},{"title":{"ja":"戦略的TR推進による自立循環型新規医療創出拠点の実現","en":"Development of a treatment for amyotrophic lateral sclerosis through improvement of ribosomal function within neurons"},"agency":{"ja":"日本医療研究開発機構（AMED）橋渡し研究プログラム","en":"Translational Research Program, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP20lm0203007"]},{"title":{"ja":"リボソームの機能改善を目指した筋萎縮性側索硬化症(ALS)の新規治療法の開発","en":"Development of a novel treatment for amyotrophic lateral sclerosis (ALS) aimed at improving ribosomal function"},"agency":{"ja":"日本医療研究開発機構（AMED） 難治性疾患実用化研究事業","en":"Practical Research Project for Rare / Intractable Diseases, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP21ek0109520"]},{"title":{"ja":"制御性T細胞を介した筋萎縮性側索硬化症の病態機序の解明と治療法の開発","en":"Elucidation of pathogenesis mechanisms and development of therapeutic approaches for amyotrophic lateral sclerosis mediated by regulatory T cells"},"agency":{"ja":"日本医療研究開発機構（AMED）脳とこころの研究推進プログラム","en":"Brain and Mind Research Promotion Program, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP23wm0525029"]},{"title":{"ja":"筋萎縮性側索硬化症（ALS）の内在性レトロウイルス（ERV）を軸とした病態解明と治療法開発","en":"Elucidation of Pathogenesis and Development of Therapeutic Approaches for Amyotrophic Lateral Sclerosis (ALS) Centered on Endogenous Retroviruses (ERVs)"},"agency":{"ja":"大阪大学先導的学際研究機構 生命医科学融合フロンティア研究部門","en":"Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University"},"grantIds":null}],"relatedPublications":[{"title":"piRNA/PIWI Protein Complex as a Potential Biomarker in Sporadic Amyotrophic Lateral Sclerosis","doi":"https://doi.org/10.1007/s12035-021-02686-2","datasets":["JGAD000993"]},{"title":"Alternative Splicing Alterations in Patients With Amyotrophic Lateral Sclerosis: Link to the Disruption of TAR DNA-Binding Protein 43 kDa Functions","doi":"https://doi.org/10.1111/ncn3.12880","datasets":["JGAD000993"]},{"title":"Single-nucleus multiome shows motor neuron glutamate overactivation in amyotrophic lateral sclerosis","doi":"https://doi.org/10.1093/brain/awaf426","datasets":["JGAD000994"]}],"datasets":["JGAD000993","JGAD000994"],"controlledAccessUsers":[]}