Potential protective effects of autophagy activated in MPP+ treated astrocytes

Abstract

Astrocytes, which have various important functions, have previously been associated with Parkinson's disease (PD), particularly in 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models of PD. MPP+ is the toxic metabolite of MPTP and is generated by the enzymatic activity of monoamine oxidase B, which is predominantly located in astrocytes. MPP+ acts as a mitochondrial complex I inhibitor. Autophagy is an evolutionarily conserved self-digestion pathway in eukaryotic cells, which occurs in response to various types of stress, including starvation and oxidative stress. Lithium treatment has previously been shown to induce autophagy in astrocytes by inhibiting the enzyme inositol monophosphatase, which may aid in the treatment of neurodegenerative diseases, including Huntington's disease, in which the toxic protein is an autophagy substrate. Therefore, using western blotting and MTT assay, the present study aimed to investigate the protective effects of lithium-induced autophagy against astrocyte injury caused by MPP+ treatment, as well as the potential underlying mechanisms. The results of the present study suggested that lithium was able to induce autophagy in astrocytes treated with MPP+, and this likely occurred via activation of the phosphoinositide 3-kinase/AKT pathway.