Abstract
Alzheimer’s disease (AD) is the most common age-associated dementia with complex pathological hallmarks. Mitochondrion, synaptosome, and myelin sheath appear to be vulnerable and play a key role in the pathogenesis of AD. To clarify the early mechanism associated with AD, followed by subcellular components separation, we performed iTRAQ (isobaric tags for relative and absolute quantification)-based proteomics analysis to simultaneously investigate the differentially expressed proteins (DEPs) within the mitochondria, synaptosome, and myelin sheath in the cerebrum of the 6-month-old triple transgenic AD (3 × Tg-AD) and 6-month-old wild-type (WT) mice. A large number of DEPs between the AD and WT mice were identified. Most of them are related to mitochondria and synaptic dysfunction and cytoskeletal protein change. Differential expressions of Lrpprc, Nefl, and Sirpa were verified by Western blot analysis. The results suggest that decreased energy metabolism, impaired amino acid metabolism and neurotransmitter synthesis, increase compensatory fatty acid metabolism, up-regulated cytoskeletal protein expression, and oxidative stress are the early events of AD. Among these, mitochondrial damage, synaptic dysfunction, decreased energy metabolism, and abnormal amino acid metabolism are the most significant events. The results indicate that it is feasible to separate and simultaneously perform proteomics analysis on the three subcellular components.
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All raw data have been deposited as online resource to the Figshare database with the name: “Proteomics Profiling of Cerebrum Mitochondria, Myelin Sheath and Synaptosome Revealed Mitochondrial Damage and Synaptic Impairments in Association with 3 × Tg‐AD Mice Model.” (https://doi.org/10.6084/m9.figshare.12949313.v1).
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Acknowledgements
The authors are grateful to Shuiming Li for his technical assistance and instrument analysis center of Shenzhen University and Kamran Ullah for revising the manuscript as well.
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This study was financially supported by the National Natural Science Foundation of China (Grant No. 31870825), the Shenzhen Bureau of Science, Technology and Information (Nos. JCYJ20180507182417779, JCYJ20170412110026229), Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions (Grant No. 2019SHIBS0003), and National Key Research and Development Program of China (Grant No. 2018YFE0118900).
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Shen, L., Yang, A., Chen, X. et al. Proteomic Profiling of Cerebrum Mitochondria, Myelin Sheath, and Synaptosome Revealed Mitochondrial Damage and Synaptic Impairments in Association with 3 × Tg‐AD Mice Model. Cell Mol Neurobiol 42, 1745–1763 (2022). https://doi.org/10.1007/s10571-021-01052-z
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DOI: https://doi.org/10.1007/s10571-021-01052-z