Graphene oxide enhances β-amyloid clearance by inducing autophagy of microglia and neurons

Abstract

Alzheimer's disease (AD) is a common neurodegenerative disease, and its pathogenesis is closely related to β-amyloid (Aβ) peptide. The deposition of Aβ in the brain due to impaired Aβ clearance is considered as an important cause of AD. The decrease in Aβ clearance is closely related to the autophagy dysfunction in brains of AD patients. It is feasible to treat AD by increasing the autophagy level of cells such as microglia and neurons to accelerate Aβ clearance. In this article we explored the ability of graphene oxide (GO) to clear Aβ through activating autophagy. Our work demonstrated that GO could inhibit the mTOR signaling pathway by activating AMPK to induce the autophagy of microglial and neurons. As expected, with the improvement of autophagy ability of microglia, GO promoted microglia-mediated Aβ phagocytosis. Under the conditions of co-culture of microglia and neurons, GO induced the autophagy of microglia and neurons, especially the autophagy of microglia, thereby promoting the clearance of Aβ, and ultimately achieved the effect of protecting neurons. Moreover, GO was not only non-cytotoxic to microglia and neurons but also able to reduce the toxicity of Aβ to neurons through its clearance. These results have shown the potential of GO in treating Alzheimer's disease.