Neuregulin-1 (Nrg1) signaling has a preventive role and is altered in the frontal cortex under the pathological conditions of Alzheimer's disease

神经调节蛋白-1 (Nrg1) 信号具有预防作用,在阿尔茨海默病的病理条件下,额叶皮质中的神经调节蛋白-1 (Nrg1) 信号会发生改变

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作者:Qiong Jiang, Shuangxi Chen, Chengliang Hu, Peizhi Huang, Huifan Shen, Weijiang Zhao

Abstract

Alzheimer's disease (AD), one of the neurodegenerative disorders that may develop in the elderly, is characterized by the deposition of β‑amyloid protein (Aβ) and extensive neuronal cell death in the brain. Neuregulin‑1 (Nrg1)‑mediated intercellular and intracellular communication via binding to ErbB receptors regulates a diverse set of biological processes involved in the development of the nervous system. In the present study, a linear correlation was identified between Nrg1 and phosphorylated ErbB (pNeu and pErbB4) receptors in a human cortical tissue microarray. In addition, increased expression levels of Nrg1, but reduced pErbB receptor levels, were detected in the frontal lobe of a patient with AD. Western blotting and immunofluorescence staining were subsequently performed to uncover the potential preventive role of Nrg1 in cortical neurons affected by the neurodegenerative processes of AD. It was observed that the expression of Nrg1 increased as the culture time of the cortical neurons progressed. In addition, H2O2 and Aβ1‑42, two inducers of oxidative stress and neuronal damage, led to a dose‑dependent decrease in Nrg1 expression. Recombinant Nrg1β, however, was revealed to exert a pivotal role in preventing oxidative stress and neuronal damage from occurring in the mouse cortical neurons. Taken together, these results suggest that changes in Nrg1 signaling may influence the pathological development of AD, and exogenous Nrg1 may serve as a potential candidate for the prevention and treatment of AD.

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