期刊
CELLS
卷 10, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/cells10071583
关键词
Alzheimer's disease; mRNA splicing; neurodegeneration; proteogenomics
类别
资金
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil (CAPES) [001]
- Research Support Foundation of the State of Rio de Janeiro (FAPERJ) [E-26/202.658/2018]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [301707/2017-0, 308697/2019-7, 442421/2019-2, 436459/2018-3]
Using a proteogenomics strategy, this study identified orthologous AS proteoforms between humans and mice. Identical proteotypic peptides of six orthologous AS proteoforms were found in both species and validated at the transcript level. Additionally, higher abundances of certain proteoforms were detected in an AD mouse model, suggesting a potential role in amyloid-like aggregate formation. This study provides valuable insights for future neurodegenerative disease research using mouse models.
Alternative splicing (AS) may increase the number of proteoforms produced by a gene. Alzheimer's disease (AD) is a neurodegenerative disease with well-characterized AS proteoforms. In this study, we used a proteogenomics strategy to build a customized protein sequence database and identify orthologous AS proteoforms between humans and mice on publicly available shotgun proteomics (MS/MS) data of the corpus callosum (CC) and olfactory bulb (OB). Identical proteotypic peptides of six orthologous AS proteoforms were found in both species: PKM1 (gene PKM/Pkm), STXBP1a (gene STXBP1/Stxbp1), Isoform 3 (gene HNRNPK/Hnrnpk), LCRMP-1 (gene CRMP1/Crmp1), SP3 (gene CADM1/Cadm1), and PKC beta II (gene PRKCB/Prkcb). These AS variants were also detected at the transcript level by publicly available RNA-Seq data and experimentally validated by RT-qPCR. Additionally, PKM1 and STXBP1a were detected at higher abundances in a publicly available MS/MS dataset of the AD mouse model APP/PS1 than its wild type. These data corroborate other reports, which suggest that PKM1 and STXBP1a AS proteoforms might play a role in amyloid-like aggregate formation. To the best of our knowledge, this report is the first to describe PKM1 and STXBP1a overexpression in the OB of an AD mouse model. We hope that our strategy may be of use in future human neurodegenerative studies using mouse models.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据