It　is　widely　accepted　that　accumulation　of　extracellular　glutamate　mediates　neuronal　injuries　in　a　number　of　neurological　disorders　via　binding　glutamate　receptors.　However,　usage　of　the　glutamate　receptor　antagonists　aimed　to　prevent　glutamate　excitotoxicity　is　still　controversial.　As　a　polyphenol　natural　product,　curcumin,　has　been　implied　multiple　bioactivities.　In　this　study,　we　explored　whether　the　silent　information　regulator　1　(　SIRT1)-　peroxisome　proliferator-　activated　receptor-　coactivator　1　alpha　(　PGC1　alpha)　pathway　participated　in　the　protection　of　curcumin　against　glutamate　excitotoxicity.　The　cultured　primary　cortical　neurons　were　treated　with　glutamate　to　set　up　a　neuronal　excitotoxicity　model.　The　MTT　and　TUNEL　methods　were　employed　to　measure　cell　viability　and　apoptosis,　respectively.　The　mitochondrial　function,　the　expression　levels　of　SIRT1,　PGC1　alpha　and　acetylated　PGC1　alpha　(ac-PGC1　alpha)　were　measured　to　explore　the　mechanism　of　curcumin　against　glutamate　excitotoxicity.　The　results　showed　that　glutamate　significantly　induced　cell　death　and　apoptosis,　which　was　blocked　by　pretreatment　with　curcumin.　Meanwhile,　curcumin　preserved　mitochondrial　function,　increased　the　expression　level　of　SIRT1　and　reduced　the　level　of　ac-PGC1　alpha　in　the　presence　of　glutamate.　These　results　suggest　that　SIRT1　mediated　deacetylation　of　PGC1a　attributes　to　the　neuroprotection　of　curcumin　against　glutamate　excitotoxicity.　(C)　2016　Elsevier　Inc.　All　rights　reserved.