Affiliations: [a] Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing, China | [b] College of Arts and Sciences, Beijing Union University, Beijing, China
Correspondence:
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Corresponding authors: Prof. Zhao-Feng Jiang, Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing United University, Beijing 100083, China. Tel.: +86 10 64900138; Fax: +86 10 64900143; E-mail: [email protected]. Han-Chang Huang, Assistant Researcher, Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing United University, Beijing 100083, China. Tel.: +86 10 62004534 8105; E-mail: [email protected].
Abstract: The neuropathology associated with Alzheimer's disease (AD) is characterized by the presence of extracellularly neuritic plaques, intracellularly neurofibrillary tangles and the loss of basal forebrain cholinergic neurons. The neuritic plaque is composed of a core of amyloid-β peptide (Aβ) while the neurofibrillary tangles contain phosphorylated tau protein, and, as such, both Aβ and tau are important molecules associated with AD. In healthy human bodies, clearance mechanisms for Aβ are available; yet if clearance fails, Aβ accumulates, increasing the risk of neurotoxicity in the brain. Tau, one of the main microtubule-associated proteins, will be hyperphosphorylated and lose the ability to bind microtubules when the homeostasis of phosphorylation and dephosphorylation is disturbed in neurons. Accumulated Aβ and hyperphosphorylated tau are thought to be coexistent. Research on the pathological changes in AD indicates that accumulated Aβ in vivo may initiate the hyperphosphorylation of tau. Also, the signal transduction pathways of tau hyperphosphorylation may be related to accumulated Aβ. In this review, we will discuss how Aβ accumulates, how tau protein is hyperphosphorylated, and how accumulated Aβ initiates hyperphosphorylation of tau protein in AD.
Keywords: α7nAChR, amyloid-β peptide (Aβ), oxidative stress, PI3K/Akt, tau protein
