Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery
| العنوان: | Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery |
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| المؤلفون: | Junmin Peng, David Vanderwall, Kaushik Kumar Dey, Hong Wang, Suresh Poudel, Ka Yang, Xusheng Wang, Bing Bai, Yuxin Li, Ping-Chung Chen |
| المصدر: | Molecular Neurodegeneration Molecular Neurodegeneration, Vol 16, Iss 1, Pp 1-16 (2021) |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Proteomics, Proteome, Amyloid, PTM, Systems biology, Review, Pathogenesis, Computational biology, Biology, Amyloidome, Cellular and Molecular Neuroscience, Biomarker discovery, RC346-429, Molecular Biology, Gene, Mass spectrometry, RC952-954.6, Biomarker, Phenotype, Geriatrics, Abeta, Biomarker (medicine), Neurology. Diseases of the nervous system, Neurology (clinical), Tau, Alzheimer’s disease |
| الوصف: | Mass spectrometry-based proteomics empowers deep profiling of proteome and protein posttranslational modifications (PTMs) in Alzheimer’s disease (AD). Here we review the advances and limitations in historic and recent AD proteomic research. Complementary to genetic mapping, proteomic studies not only validate canonical amyloid and tau pathways, but also uncover novel components in broad protein networks, such as RNA splicing, development, immunity, membrane transport, lipid metabolism, synaptic function, and mitochondrial activity. Meta-analysis of seven deep datasets reveals 2,698 differentially expressed (DE) proteins in the landscape of AD brain proteome (n = 12,017 proteins/genes), covering 35 reported AD genes and risk loci. The DE proteins contain cellular markers enriched in neurons, microglia, astrocytes, oligodendrocytes, and epithelial cells, supporting the involvement of diverse cell types in AD pathology. We discuss the hypothesized protective or detrimental roles of selected DE proteins, emphasizing top proteins in “amyloidome” (all biomolecules in amyloid plaques) and disease progression. Comprehensive PTM analysis represents another layer of molecular events in AD. In particular, tau PTMs are correlated with disease stages and indicate the heterogeneity of individual AD patients. Moreover, the unprecedented proteomic coverage of biofluids, such as cerebrospinal fluid and serum, procures novel putative AD biomarkers through meta-analysis. Thus, proteomics-driven systems biology presents a new frontier to link genotype, proteotype, and phenotype, accelerating the development of improved AD models and treatment strategies. Supplementary Information The online version contains supplementary material available at 10.1186/s13024-021-00474-z. |
| تدمد: | 1750-1326 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9e76a69583af276d3a6710ff6dc7be66 https://doi.org/10.1186/s13024-021-00474-z |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9e76a69583af276d3a6710ff6dc7be66 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 17501326 |
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