Amyloid-β1-42 dynamically regulates the migration of neural stem/progenitor cells via MAPK-ERK pathway

Publication date: Available online 3 November 2018Source: Chemico-Biological InteractionsAuthor(s): Zhu Wang, Yantian Chen, Xueyi Li, Pinky Sultana, Ming Yin, Zejian WangAbstractNeural stem/progenitor cell (NSPC) based therapy represents an attractive treatment for Alzheimer's disease (AD), the most common neurodegenerative disorder with no effective treatment to date. This can be achieved by stimulating endogenous NSPCs and/or administrating exogenously produced NSPCs. Successful repair requires the migration of NSPCs to the loci where neuronal loss occurs, differentiation and integration into neural networks. However, the progressive loss of neurons in the brain of AD patients suggests that the repair by endogenous NSPCs in the setting of AD may be defective. The production and deposition of amyloid-β1-42 (Aβ1-42) peptides is thought to be a central event in the pathogenesis of AD. Here we report that Aβ1-42 peptides inhibit the migration of in vitro cultured NSPCs by disturbing the ERK-MAPK signal pathway. We found that the migratory capacity of NSPCs was compromised upon treatment with oligomeric Aβ1-42; the inhibitory effect occurred in a dose-dependent manner. Our previous studies have shown that Aβ1-42 triggers the expression of GRK2 by unknown mechanism. Herein we found that the Aβ1-42 evoked upregulation of GRK2 expression was attenuated upon treatment with the ERK inhibitor SCH772984 at 2.5 μM, but not with inhibitors for p38 or JNK. We detected a dose-depe...
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research