Proteomic Analysis Reveals Physiological Activities of Aβ Peptide for Alzheimer’s Disease

Author:

Ai Xiaorui12,Cao Zeyu12,Ma Zhaoru12,Liu Qinghuan12,Huang Wei12,Sun Taolei12,Li Jing12ORCID,Yang Chenxi3ORCID

Affiliation:

1. School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China

2. Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases, Wuhan University of Technology, 122 Luoshi Road, Wuhan 430070, China

3. School of Biological Science & Medical Engineering, Southeast University, No. 2 Sipailou, Nanjing 210096, China

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 Aβ40 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 Aβ1-40 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 Aβ40 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, Aβ40 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.

Funder

National Natural Science Foundation of China

Fundamental Research Funds for the Central Universities

Publisher

MDPI AG

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