期刊
OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY
卷 26, 期 1, 页码 51-63出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/omi.2021.0173
关键词
neurodegeneration; Alzheimer's disease model; Drosophila melanogaster; amyloid toxicity; quantitative proteomics; drug targets
资金
- Karnataka Biotechnology and Information Technology Services (KBITS)
- Center for Systems Biology and Molecular Medicine at Yenepoya (Deemed to be University), Mangalore
- Biotechnology Skill Enhancement Programme in Multiomics Technology [ITD 02MDA2017]
- Biotechnology Skill Enhancement Programme (BiSEP)
- Senior Research Fellowship from the Indian Council of Medical Research (ICMR)
- Senior Research Fellowship from the University Grants Commission (UGC), Government of India
Using quantitative proteomics, this study identified significantly altered proteins and post-translational modifications associated with Aβ42 expression in a D. melanogaster model for AD. These proteins are involved in biological processes related to neuronal damage, neuroplasticity, and AD progression. The findings provide new insights into altered protein dynamics relevant to AD pathogenesis.
Production and deposition of beta-amyloid peptides (A beta) are among the major hallmarks of the pathogenesis of Alzheimer's disease (AD). Mapping the altered protein dynamics associated with A beta accumulation and neuronal damage may open up new avenues to innovation for drug target discovery in AD. Using quantitative proteomics, we report new findings from the amyloid beta-peptide with 42 amino acids (A beta 42) expressing Drosophila melanogaster model for AD compared to that of the wild-type flies. We identified 302,241 peptide-spectrum matches with 25,641 nonredundant peptides corresponding to 7959 D. melanogaster proteins. Furthermore, we unraveled 538 significantly altered proteins in A beta 42 expressing flies. These differentially expressed proteins were enriched for biological processes associated with neuronal damage leading to AD progression. We also identified 463 unique post-translational modification events mapping to 202 proteins from the same dataset. Among these, 303 modified peptides corresponding to 246 proteins were also altered in the AD model. These modified proteins are known to be involved in the disruption of molecular functions maintaining neuronal plasticity. This study provides new molecular leads on altered protein dynamics relevant to neurodegeneration, neuroplasticity, and AD progression induced by A beta 42 toxicity. These proteins may prove useful to discover new drugs in an AD model of D. melanogaster and evaluate their efficacy and mode of molecular action in the future.
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