Abstract
Alzheimer’s disease (AD) is a chronic progressive degenerative disease of the nervous system. Its pathogenesis is complex and is related to the abnormal expression of the amyloid β (Aβ), APP, and Tau proteins. Evidence has demonstrated that bone morphogenetic protein 4 (BMP4) is highly expressed in transgenic mouse models of AD and that endogenous levels of BMP4 mainly affect hippocampal function. To determine whether BMP4 participates in AD development, transgenic mice were constructed that overexpress BMP4 under the control of the neuron-specific enolase (NSE) promoter. We also performed MTT, FACS, transfection, TUNEL, and Western blotting assays to define the role of BMP4 in cells. We found that middle-aged BMP4 transgenic mice exhibited impaired memory via the Morris water maze experiment. Moreover, their hippocampal tissues exhibited high expression levels of AD-related proteins, including APP, Aβ, PSEN-1, Tau, P-Tau (Thr181), and P-Tau (Thr231). Furthermore, in multiple cell lines, the overexpression of BMP4 increased the expression of AD-related proteins, whereas the downregulation of BMP4 demonstrated opposing effects. Consistent with these results, BMP4 modulation affected cell apoptosis via the regulation of BAX and Bcl-2 expression in cells. Our findings indicate that BMP4 overexpression might be a potential factor to induce AD.
Highlights
The misfolding and aggregation of certain proteins are fundamental features of neurodegenerative diseases, such as Alzheimer’s disease (AD)
We have constructed transgenic mice overexpressing bone morphogenetic protein 4 (BMP4) under the control of the neuron-specific enolase (NSE) promoter, and we used these mice to determine the function of BMP4 in brain development and AD progression
In this study, we explored the role of BMP4 in AD development and progression
Summary
The misfolding and aggregation of certain proteins are fundamental features of neurodegenerative diseases, such as Alzheimer’s disease (AD). AD is an age-related, progressive, irreversible neurodegenerative disease that leads to the loss of selected neurons in the basal forebrain, almond nucleus, hippocampus, and cortex, as well as the progressive deceleration of cognition and memory[1,2,3,4]. The main manifestations of AD are progressive memory impairment, cognitive impairment, personality changes, language disorders, and other neurological symptoms[5]. The hippocampus is a critical brain region for learning and memory and is vulnerable to damage in the early stages of AD. Emerging evidence suggests that neurogenesis in the adult hippocampus is an early critical event in the AD process[6]. AD is characterized by the insidious development of hippocampal pathology[7]
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