Proteomic analysis to identify the pathways and processes affected by altered levels of Sideroflexin3 (SFXN3) in the synapse.

Proteomic data from TMT based analysis of synapses biochemically isolated from Sfxn3-KO mice (http://www.mousephenotype.org/data/genes/MGI:2137679). See attached word/.txt description for further information. Briefly - Synapses are a primary pathological target in neurodegenerative diseases. Identifying therapeutic targets at the synapse could delay progression of numerous conditions. The mitochondrial protein SFXN3 is a neuronally-enriched protein expressed in synaptic terminals and regulated by key synaptic proteins, including alpha-synuclein (previously reported in Amorim et al., 2017 [PMID:28049726] and Graham et al., 2017 [PMID: 29078798]). Applying high-resolution proteomics to synapses biochemically isolated from Sfxn3-KO mice (http://www.mousephenotype.org/data/genes/MGI:2137679), we sought to identify what the molecular consequences of altered SFXN3 expression are in vivo. Analysis of the data contained within this submission suggest that Sfxn3 regulates proteins and pathways associated with neurodegeneration and cell death (including CSP alpha and caspase-3), as well as cascades altered in other neurological conditions (including Parkinson’s disease and Alzheimer’s disease).

本数据集源自对Sfxn3基因敲除（Sfxn3-KO）小鼠生化分离突触开展的基于串联质量标签（TMT）的蛋白质组学分析，相关小鼠基因信息可参见：http://www.mousephenotype.org/data/genes/MGI:2137679。详细信息请参阅附件中的Word/文本描述文件。
简言之，突触是神经退行性疾病的核心病理靶点，在突触层面鉴定治疗靶点有望延缓多种相关疾病的病程进展。线粒体蛋白SFXN3是一种神经元富集蛋白，表达于突触前末梢，且受包括α-突触核蛋白在内的关键突触蛋白调控（相关研究成果已先期发表于Amorim等2017年的研究[PMID:28049726]及Graham等2017年的研究[PMID:29078798]）。本研究通过对上述Sfxn3-KO小鼠生化分离的突触应用高分辨率蛋白质组学技术，旨在明确体内SFXN3表达异常所产生的分子层面效应。对本提交数据的分析结果显示，Sfxn3可调控与神经退行性变及细胞死亡相关的蛋白与通路（包括CSPα与半胱天冬酶-3），同时还可调控其他神经系统疾病（如帕金森病与阿尔茨海默病）中发生异常改变的信号级联反应。