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Proteomic Analysis Reveals Physiological Activities of Aβ Peptide for Alzheimer's Disease.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 Jul 30; Vol. 25 (15). Date of Electronic Publication: 2024 Jul 30. - Publication Year :
- 2024
-
Abstract
- With the rapid progress in deciphering the pathogenesis of Alzheimer's disease (AD), it has been widely accepted that the accumulation of misfolded amyloid β (Aβ) in the brain could cause the neurodegeneration in AD. Although much evidence demonstrates the neurotoxicity of Aβ, the role of Aβ in the nervous system are complex. However, more comprehensive studies are needed to understand the physiological effect of Aβ <subscript>40</subscript> monomers in depth. To explore the physiological mechanism of Aβ, we employed mass spectrometry to investigate the altered proteomic events induced by a lower submicromolar concentration of Aβ. Human neuroblastoma SH-SY5Y cells were exposed to five different concentrations of Aβ <subscript>1-40</subscript> monomers and collected at four time points. The proteomic analysis revealed the time-course behavior of proteins involved in biological processes, such as RNA splicing, nuclear transport and protein localization. Further biological studies indicated that Aβ <subscript>40</subscript> monomers may activate PI3K/AKT signaling to regulate p-Tau, Ezrin and MAP2. These three proteins are associated with dendritic morphogenesis, neuronal polarity, synaptogenesis, axon establishment and axon elongation. Moreover, Aβ <subscript>40</subscript> monomers may regulate their physiological forms by inhibiting the expression of BACE1 and APP via activation of the ERK1/2 pathway. A comprehensive exploration of pathological and physiological mechanisms of Aβ is beneficial for exploring novel treatment.
- Subjects :
- Humans
Cell Line, Tumor
Aspartic Acid Endopeptidases metabolism
Aspartic Acid Endopeptidases genetics
Peptide Fragments metabolism
Amyloid Precursor Protein Secretases metabolism
Cytoskeletal Proteins metabolism
Cytoskeletal Proteins genetics
tau Proteins metabolism
Phosphatidylinositol 3-Kinases metabolism
Signal Transduction
Proto-Oncogene Proteins c-akt metabolism
Amyloid beta-Protein Precursor metabolism
Proteome metabolism
Microtubule-Associated Proteins metabolism
MAP Kinase Signaling System
Amyloid beta-Peptides metabolism
Alzheimer Disease metabolism
Alzheimer Disease pathology
Proteomics methods
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 39125907
- Full Text :
- https://doi.org/10.3390/ijms25158336