【摘 要】
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My research goal is to develop mass spectrometry-based proteomics and systems biology approaches to address biomedical challenges.Wehave developed a quantitative proteomics pipeline,capable of analyzi
【机 构】
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St.Jude Medical Center
【出 处】
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第九届海内外华人神经科学家研讨会(The 9th Symposium for Chinese Neuroscientis
论文部分内容阅读
My research goal is to develop mass spectrometry-based proteomics and systems biology approaches to address biomedical challenges.Wehave developed a quantitative proteomics pipeline,capable of analyzing >10,000 proteins and dissecting tens of thousands of posttranslational modifications from relevant cellular and animal models as well as human clinical specimens.Integration of such large-scale omics data offers a holistic view for unbiased identification of central disease gene/protein networks.To understand the pathogenesis of Alzheimer disease(AD),the most common form of dementia,we profiled aggregated proteome in all common neurodegenerative diseases,including AD,mild cognitive impairment,Parkinson disease,Lewy body dementia,Ub-positive frontotemporal lobar degeneration,amyotrophic lateral sclerosis,and corticobasal degeneration.This comprehensive study identified the accumulation of U1-70K and other U1 snRNP spliceosome components in AD.Multiple U1 snRNP subunits form cytoplasmic tangle-like structures in AD but not in other diseases.RNAseq analysis reveals dysregulated RNA processing with accumulation of unspliced RNA species in AD.Thus,our results demonstrate unique U1 snRNP pathology and suggest abnormal RNA splicing in AD.Furthermore,we have generated a brain-specific transgenic mouse model for deregulating the U1-70K activity.The transgenic mice recapitulate many AD features,supporting the role of RNA dysregulation in Alzheimers disease.
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