Alpha-synuclein oligomer-selective antibodies reduce intracellular accumulation and mitochondrial impairment in alpha-synuclein exposed astrocytes

Background: due to its neurotoxic properties,oligomeric alpha-synuclein (α-syn) has been suggested as an attractive target for passive immunization against parkinson's disease (pd). in mouse models of pd,antibody treatment has been shown to lower the levels of pathogenic α-syn species,including oligomers,although the mechanisms of action remain unknown. we have previously shown that astrocytes rapidly engulf α-syn oligomers that are intracellularly stored,rather than degraded,resulting in impaired mitochondria. methods: the aim of the present study was to investigate if the accumulation of α-syn in astrocytes can be affected by α-syn oligomer-selective antibodies. co-cultures of astrocytes,neurons,and oligodendrocytes were derived from embryonic mouse cortex and exposed to α-syn oligomers or oligomers pre-incubated with oligomer-selective antibodies. results: in the presence of antibodies,the astrocytes displayed an increased clearance of the exogenously added α-syn,and consequently,the α-syn accumulation in the culture was markedly reduced. moreover,the addition of antibodies rescued the astrocytes from the oligomer-induced mitochondrial impairment. conclusions: our results demonstrate that oligomer-selective antibodies can prevent α-syn accumulation and mitochondrial dysfunction in cultured astrocytes. © 2017 the author(s).