BACKGROUND: @entity191 ( @entity191 ) is a progressive @entity179 characterized by loss of @entity935 neurons in the substantia nigra pars compacta (SNpc) and widespread aggregates of the protein @entity8095 ( @entity8095 ). Increasing evidence points to @entity32 as a chief mediator; however, the role of @entity8095 in triggering and sustaining @entity32 remains unclear. In models of @entity195 ( @entity195 ), @entity15 ( @entity15 ) and @entity2359 models of @entity191 , the chemokine CX3CL1 (fractalkine) and its receptor ( @entity9173 ) have important roles in modulating neuroinflammation. METHODS: To examine the role of fractalkine signaling in @entity8095 -induced-neuroinflammation and neurodegeneration, we used an in vivo @entity19 model in which @entity1 @entity8095 is overexpressed by an adeno associated viral vector serotype 2 ( @entity4700 ) and in vitro phagocytosis and protein internalization assays with primary microglia treated with aggregated @entity8095 . RESULTS: We observed that loss of @entity9173 expression led to a reduced inflammatory response, with reduced IgG deposition and expression of MHCII 4 weeks post-transduction. Six months post transduction, @entity4700 mediated overexpression of @entity8095 leads to loss of dopaminergic neurons, and this loss was not exacerbated in animals with deletion of @entity9173 . To determine the mechanism by which @entity9173 affects inflammatory responses in @entity8095 -induced @entity32 , phagocytosis was assessed using a fluorescent microsphere assay as well as by microglial uptake of aggregated @entity8095 . @entity9173 -/- microglia showed reduced uptake of fluorescent beads and aggregated @entity8095 . CONCLUSION: Our results suggest that one mechanism by which @entity9173 -/- attenuates @entity32 is at the level of phagocytosis of aggregated @entity8095 by microglia. These data implicate fractalkine signaling as a potential therapeutic target for regulating inflammatory response in @entity8095 models @entity191 .

Fractalkine Signaling Regulates the Inflammatory Response in an a-Synuclein Model of XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity8095 :: ('6622', 'Gene') :: ['a-syn', 'alpha-synuclein'] @entity935 :: ('MESH:D004298', 'Chemical') :: ['dopamine'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity191 :: ('MESH:D010300', 'Disease') :: ['Parkinson disease', 'PD'] @entity179 :: ('MESH:D019636', 'Disease') :: ['neurodegenerative disorder'] @entity9173 :: ('1524', 'Gene') :: ['CX3CR1'] @entity195 :: ('MESH:D000544', 'Disease') :: ['AD', "Alzheimer's disease"] @entity4700 :: ('10804', 'Species') :: ['AAV2'] @entity15 :: ('MESH:D009103', 'Disease') :: ['MS', 'multiple sclerosis'] @entity2359 :: ('MESH:D020258', 'Disease') :: ['neurotoxin']
@entity191 :: (MESH:D010300,Disease) :: ['Parkinson Disease']
