Abstract
Bcl-2-associated athanogene 2 (BAG2) is an important member in the BAG family which is characterized by their property of interaction with a variety of partners involved in modulating the proliferation/death balance. The role of BAG family proteins in Parkinson’s disease (PD) has not been elucidated. In this study, we demonstrated that overexpressing BAG2 ameliorates the effects of 1-methyl-4-phenylpyridinium (MPP+) in mitochondrial membrane potential (MMP) collapse, reactive oxygen species (ROS) generation, and mitochondrial release of cytochrome C. However, knockdown of DJ-1 abolished the neuroprotective effects of BAG2 against MPP+-induced neuronal toxicity. With co-immunoprecipitation and pulldown experiments, we present a direct physical interaction between BAG2 and DJ-1. Co-expression of BAG-2 together with DJ-1 increased the ratio of dimer/monomer staining intensity at the basal level. Our results indicated that MPP+ treatment leads to the disassociation of the homodimer of DJ-1. When BAG2 was overexpressed in cells, the homodimer of DJ-1 was increased. Importantly, BAG2 prevents MPP+-induced monomerization of DJ-1. Thus, our data showed that the neuroprotective effects of BAG2 are mediated by its interaction with DJ-1, strengthening the link between the BAG proteins and PD-related neurodegeneration.
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Shandong Province medicine and health science and technology development project, 2013WSB02001
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Song, Z., Xu, S., Song, B. et al. Bcl-2-Associated Athanogene 2 Prevents the Neurotoxicity of MPP+ via Interaction with DJ-1. J Mol Neurosci 55, 798–802 (2015). https://doi.org/10.1007/s12031-014-0481-6
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DOI: https://doi.org/10.1007/s12031-014-0481-6