Improvement of spinal muscular atrophy via correction of the SMN2 splicing defect by Brucea javanica (L.) Merr. extract and Bruceine D = 아담자 및 bruceine D의 척수성 근위축 개선효능

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dc.contributor.authorJiyeon Baek-
dc.contributor.authorHyejeong Jeong-
dc.contributor.authorYeongwook Ham-
dc.contributor.authorYang Hee Jo-
dc.contributor.authorMiri Choi-
dc.contributor.authorMingu Kang-
dc.contributor.authorBora Son-
dc.contributor.authorSangho Choi-
dc.contributor.authorHyung Won Ryu-
dc.contributor.authorJanghwan Kim-
dc.contributor.authorH Shen-
dc.contributor.authorK Sydara-
dc.contributor.authorSang Woo Lee-
dc.contributor.authorSoo Yong Kim-
dc.contributor.authorS B Han-
dc.contributor.authorSei-Ryang Oh-
dc.contributor.authorSungchan Cho-
dc.description.abstractBACKGROUND: Spinal muscular atrophy (SMA) is a rare neuromuscular disease and a leading genetic cause of infant mortality. SMA is caused primarily by the deletion of the survival motor neuron 1 (SMN1) gene, which leaves the duplicate gene SMN2 as the sole source of SMN protein. The splicing defect (exon 7 skipping) of SMN2 leads to an insufficient amount of SMN protein. Therefore, correcting this SMN2 splicing defect is considered to be a promising approach for the treatment of SMA. PURPOSE: This study aimed to identify active compounds and extracts from plant resources to rescue SMA phenotypes through the correction of SMN2 splicing. STUDY DESIGN: Of available plant resources, candidates with SMA-related traditional medicine information were selected for screening using a robust luciferase-based SMN2 splicing reporter. Primary hits were further evaluated for their ability to correct the splicing defect and resultant increase of SMN activity in SMA patient-derived fibroblasts. Confirmed hits were finally tested to determine the beneficial effects on the severe Δ7 SMA mouse. METHODS: SMN2 splicing was analyzed using a luciferase-based SMN2 splicing reporter and subsequent RT-PCR of SMN2 mRNAs. SMA phenotypes were evaluated by the survival, body weights, and righting reflex of Δ7 SMA mice. RESULTS: In a screen of 492 selected plant extracts, we found that Brucea javanica extract and its major constituent Bruceine D have SMN2 splicing-correcting activity. Their ability to correct the splicing defect and the resulting increased SMN activity were further confirmed in SMA fibroblasts. Importantly, both B. javanica and Bruceine D noticeably improved the phenotypic defects, especially muscle function, in SMA mice. Reduced expression of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) contributed to the correction of splicing by B. javanica. CONCLUSION: Our work revealed that B. javanica and Bruceine D correct the SMN2 splicing defect and improve the symptoms of SMA in mice. These resources will provide another possibility for development of a plant-derived SMA drug candidate.-
dc.titleImprovement of spinal muscular atrophy via correction of the SMN2 splicing defect by Brucea javanica (L.) Merr. extract and Bruceine D = 아담자 및 bruceine D의 척수성 근위축 개선효능-
dc.title.alternativeImprovement of spinal muscular atrophy via correction of the SMN2 splicing defect by Brucea javanica (L.) Merr. extract and Bruceine D-
dc.contributor.affiliatedAuthorJiyeon Baek-
dc.contributor.affiliatedAuthorHyejeong Jeong-
dc.contributor.affiliatedAuthorYeongwook Ham-
dc.contributor.affiliatedAuthorYang Hee Jo-
dc.contributor.affiliatedAuthorMiri Choi-
dc.contributor.affiliatedAuthorMingu Kang-
dc.contributor.affiliatedAuthorBora Son-
dc.contributor.affiliatedAuthorSangho Choi-
dc.contributor.affiliatedAuthorHyung Won Ryu-
dc.contributor.affiliatedAuthorJanghwan Kim-
dc.contributor.affiliatedAuthorSang Woo Lee-
dc.contributor.affiliatedAuthorSoo Yong Kim-
dc.contributor.affiliatedAuthorSei-Ryang Oh-
dc.contributor.affiliatedAuthorSungchan Cho-
dc.identifier.bibliographicCitationPhytomedicine, vol. 65, pp. 153089-153089-
dc.subject.keywordAlternative splicing-
dc.subject.keywordBrucea javanica, Bruceine D-
dc.subject.keywordNeuromuscular disease-
dc.subject.keywordSpinal muscular atrophy (SMA)-
dc.subject.keywordSplicing modulator-
dc.subject.localAlternative splicing-
dc.subject.localBrucea javanica, Bruceine D-
dc.subject.localNeuromuscular disease-
dc.subject.localSpinal muscular atrophy (SMA)-
dc.subject.localSpinal muscular atrophy-
dc.subject.localSplicing modulator-
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > International Biological Material Research Center > 1. Journal Articles
Ochang Branch Institute > Natural Medicine Research Center > 1. Journal Articles
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
Ochang Branch Institute > 1. Journal Articles
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