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iTRAQ-based ProteomicAnalysis of APPSw,IndMice ProvidesInsights into theEarly Changes inAlzheimer’s Disease Nan LiPinghong HuTiantian Xu2017 год

iTRAQ-based Proteomic Analysis of APPSw,Ind Mice Provides Insights into the Early Changes in Alzheimer’s Disease
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Аннотация: Several proteins have been identified as potential diagnostic biomarkers in imaging, genetic, or proteomic studies in Alzheimer disease (AD) patients and mouse models. However, biomarkers for presymptom diagnosis of AD are still under investigation, as are the presymptom molecular changes in AD pathogenesis.In this study, we aim to analyzed the early proteomic changes in APPSw,Ind mice and to conduct further functional studies on interesting proteins.We used the isobaric tags for relative and absolute quantitation (iTRAQ) approach combined with mass spectrometry to examine the early proteomic changes in hippocampi of APPSw,Ind mice. Quantitative reverse transcription polymerase chain reaction (RT-PCR) and immuno-blotting were performed for further validation. Finally, the functions of interesting proteins β-spectrin and Rab3a in APP trafficking and processing were tested by shRNA knockdown, in N2A cells stably expressing β-amyloid precursor protein (APP).The iTRAQ and RT-PCR results revealed the detailed molecular changes in oxidative stress, myelination, astrocyte activation, mTOR signaling and Rab3-dependent APP trafficking in the early stage of AD progression. Knock down of β -spectrin and Rab3a finally led to increased APP fragment production, indicating key roles of β-spectrin and Rab3a in regulating APP processing.Our study provides the first insights into the proteomic changes that occur in the hippocampus in the early stages of the AD mouse model. In addition to improving the understanding of molecular alterations and functional cascades involved in early AD pathogenesis, our findings raise the possibility of developing potential biomarkers and therapeutic targets for early AD.
Год издания: 2017
Авторы: Nan Li, Pinghong Hu, Tiantian Xu, Huan Chen, Xiaoying Chen, Jianwen Hu, Xifei Yang, Lei Shi, Jianhong Luo, Junyu Xu
Издательство: Bentham Science Publishers
Источник: Current Alzheimer Research
Ключевые слова: Alzheimer's disease research and treatments, Mitochondrial Function and Pathology, Metabolomics and Mass Spectrometry Studies
Другие ссылки: Current Alzheimer Research (HTML)
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Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
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