Background:　Mutations　in　glucocerebrosidase　(GBA),　a　lysosomal　enzyme　are　the　most　common　genetic　risk　factor　for　developing　Parkinson＇s　disease　(PD).　We　studied　how　reduced　GCase　activity　affects　alpha-synuclein　(alpha-syn)　and　its　mutants　(A30P　and　A53T)　aggregation,　neurodegeneration,　sleep　and　locomotor　behavior　in　a　fly　model　of　PD.　Methods:　We　developed　drosophila　with　GBA　gene　knockdown　(RNAi)　(with　reduced　GCase　activity)　that　simultaneously　expresses　either　wildtype　(WT)　or　mutants　such　as　A30P　or　A53T　alpha-syn.　Western　blot　and　confocal　microscopy　were　performed　to　study　the　alpha-syn　aggregation　and　neurodegeneration　in　these　flies.　We　also　studied　the　sleep　and　locomotor　activity　of　those　flies　using　Drosophila　activity　monitor　(DAM)　system.　Results:　Western　blot　analysis　showed　that　GBA　RNAi　A53T　alpha-syn　flies　(30　days　old)　had　an　increased　level　of　Triton　insoluble　synuclein　(that　corresponds　to　alpha-syn　aggregates)　compared　to　corresponding　A53T　flies　without　GBA　RNAi　(control),　while　mRNA　expression　of　alpha-syn　remained　unchanged.　Confocal　imaging　of　whole　brain　staining　of　30　days　old　drosophila　showed　a　statistically　significant　decrease　in　neuron　numbers　in　PPL1　cluster　in　flies　expressing　alpha-syn　WT,　A30P　and　A53T　in　the　presence　GBA　RNAi　compared　to　corresponding　control.　Staining　with　conformation　specific　antibody　for　alpha-syn　aggregates　showed　an　increased　number　of　neurons　staining　for　alpha-syn　aggregates　in　A53T　fly　brain　with　GBA　RNAi　compared　to　control　A53T　flies,　thus　confirming　our　protein　analysis　finding　that　under　decreased　GBA　enzyme　activity,　mutant　A53T　aggregates　more　than　the　control　A53T　without　GBA　silencing.　Sleep　analysis　revealed　decreased　total　activity　in　GBA　silenced　flies　expressing　mutant　A53T　compared　to　both　A53T　control　flies　and　GBA　RNAi　flies　without　synuclein　expression.　Conclusion:　In　A53T　flies　with　reduced　GCase　activity,　there　is　increased　alpha-syn　aggregation　and　dopamine　(DA)　neuronal　loss.　This　study　demonstrates　that　reduced　GCase　activity　both　in　the　context　of　heterozygous　GBA1　mutation　associated　with　PD　and　in　old　age,　contribute　to　increased　aggregation　of　mutant　alpha-syn　A53T　and　exacerbates　the　phenotype　in　a　fly　model　of　PD.