Multi-omic insights into molecular mechanism and therapeutic targets in spinocerebellar ataxia type 7

被引：0

作者：

Ahn, Soo Hyun ^{[1
,2
,4
]}

Jang, Yoonhyuk ^{[1
,2
,3
,4
]}

Jang, Bum-Sup ^{[1
,4
,5
]}

Moon, Jangsup ^{[1
,2
,6
]}

Lee, Woo-Jin ^{[7
]}

Park, Dong-Kyu ^{[2
,8
]}

Yu, Jung-Suk ^{[2
,8
]}

Son, Hyoshin ^{[9
]}

Kim, Hyeyoon ^{[10
,11
]}

Han, Dohyun ^{[11
]}

Seok, Heeyoung ^{[2
,12
]}

Kim, Yongmoo ^{[1
,2
]}

Shin, Seo-Yi ^{[1
,2
]}

Lee, Soon-Tae ^{[1
,2
]}

Park, Kyung-Il ^{[3
,13
]}

Jung, Keun-Hwa ^{[1
,2
]}

Jeon, Daejong ^{[8
]}

Lee, Sang Kun ^{[1
,2
]}

Chu, Kon ^{[1
,2
]}

机构：

[1] Seoul Natl Univ, Seoul Natl Univ Hosp, Coll Med, Dept Neurol, Seoul, South Korea

[2] Seoul Natl Univ Hosp, Coll Med & Hosp, Comprehens Epilepsy Ctr, Biomed Res Inst,Ctr Med Innovat,Lab Neurotherapeut, Seoul, South Korea

[3] Seoul Natl Univ Hosp, Biomed Res Inst, Seoul 03080, South Korea

[4] Natl Strateg Technol Res Inst, Seoul 03080, South Korea

[5] Seoul Natl Univ, Seoul Natl Univ Hosp, Coll Med, Dept Radiat Oncol, Seoul, South Korea

[6] Seoul Natl Univ, Seoul Natl Univ Hosp, Coll Med, Dept Genom Med, Seoul 03080, South Korea

[7] Seoul Natl Univ, Bundang Hosp, Dept Neurol, Seongnam, South Korea

[8] Adv Neural Technol, Seoul 03087, South Korea

[9] Catholic Univ Korea, Eunpyeong St Marys Hosp, Coll Med, Dept Surg, Seoul 03312, South Korea

[10] Seoul Natl Univ Hosp, Biomed Res Inst, Prote Core Facil, Seoul 03080, South Korea

[11] Seoul Natl Univ Hosp, Dept Transdisciplinary Med, Seoul 03080, South Korea

[12] Seoul Natl Univ Hosp, Biomed Res Inst, Dept Transdisciplinary Res & Collaborat, Genom Core Facil, Seoul 03080, South Korea

[13] Seoul Natl Univ Hosp Healthcare Syst Gangnam Ctr, Dept Neurol, Seoul 06236, South Korea

来源：

MOLECULAR THERAPY NUCLEIC ACIDS | 2025年 / 36卷 / 01期

关键词：

CEREBELLAR-ATAXIA; SEROTONIN; REVEALS; EXPRESSION; BUSPIRONE; EFFICACY; SCA1; DRR1; SAGA;

D O I：

10.1016/j.omtn.2024.102414

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Recent advances in molecular science have significantly enlightened our mechanistic understanding of spinocerebellar ataxia type 7. To further close remaining gaps, we performed a multi-omics analysis using SCA7 266Q/5Q mice. Entire brain tissue samples were collected from 12-week-old mice, and RNA sequencing, methylation analysis, and proteomic analysis were performed. Results were integrated to identify genes with identical trends in expression across all three analyses. Data from RNA sequencing and methylation analysis revealed 58 significantly hypomethylated-upregulated genes and 62 hypermethylated-downregulated genes, mostly enriched in GO terms of regulation of axonogenesis, channel activity, and monoamine signaling. In the proteomic analysis, 211 upregulated and 281 downregulated DEPs associated mostly with immune response and cellular mobility were identified. Two genes, Fam107b and Tph2, showed differential expressions in both transcriptomic and proteomic analyses. Findings were validated in RT-qPCR as well as open data source analysis. Our study is the fi rst to perform multi-omics analysis in SCA7 mice and will serve as an important reference for future studies.

引用

页数：13

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