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Neuroinflammation and microglial activation are two important hallmarks of neurodegenerative diseases. Continuous microglial activation may cause the release of several cytotoxic molecules, including many cytokines that are involved in the inflammatory process. Therefore, attenuating inflammation caused by activated microglia may be an approach for the therapeutic management of neurodegenerative diseases. In addition, many studies have reported that polyphenol pentagalloyl glucose (1,2,3,4,6-penta-O-galloyl-β-D-glucose; PGG) is a molecule with potent anti-inflammatory effects, such as inhibiting the release of proinflammatory cytokines. Our previous studies revealed that PGG attenuated the expression of two inflammatory cytokines (murine monocyte chemoattractant protein-5 and pro-metalloproteinase-9) in lipopolysaccharide/interferon γ-activated BV-٢ microglial cells. Additionally, PGG modulated the NF-κB and MAPK signaling pathways by altering genes and proteins, which may affect the MAPK cascade and NF-κB activation. The aim of the present study was to investigate the ability of PGG to modulate the expression of proteins released in activated BV-2 microglial cells, which may be involved in the pathological process of inflammation and neurodegeneration. Proteomic analysis of activated BV-2 cells identified 17 proteins whose expression levels were significantly downregulated by PGG, including septin-7, ataxin-2, and adenylosuccinate synthetase isozyme 2 (ADSS). These proteins were previously described as being highly expressed in neurodegenerative diseases and/or involved in the signaling pathways associated with the formation and growth of neuronal connections and the control of Alzheimer's disease pathogenesis. The inhibitory effect of PGG on ataxin-2, septin-7 and ADSS was further confirmed at the protein and transcriptional levels. Therefore, the obtained results suggest that PGG, with its potent inhibitory effects on ataxin-2, septin-7 and ADSS, may have potential use in the therapeutic management of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]