Synucleinopathies are a group of neurodegenerative disorders characterized by the presence of aggregated and fibrillar forms of alpha-synuclein (α-syn). Here, we analyze the effect of different species of α-syn, including monomeric, oligomeric and fibrillar forms of the protein, on rat astrocytes. Astrocytes treated with these distinct forms of α-syn showed an increase in long and thin processes and glial fibrillary acidic protein expression, indicating cell activation, high levels of intracellular oxidants and increased expression of cytokines. Moreover, astrocytes incubated with the different species induced hippocampal neuronal death in co-culture, and cytotoxicity was particularly enhanced by exposure to fibrillar α-syn. Further exploration of the mechanisms behind astrocyte activation and cytotoxicity revealed differences between the assessed α-syn species. Only oligomers induced mitochondrial dysfunction in astrocytes and significantly increased extracellular hydrogen peroxide production by these cells. Besides, TNF-α and IL-1β (interleukin 1β) expression presented different kinetics and levels depending on which species induced the response. Our data suggest that α-syn species (monomeric, oligomeric and fibrillar) induce astrocyte activation that can lead to neuronal death. Nevertheless, the tested α-syn species act through different preferential mechanisms and potency. All together these results help to understand the effect of α-syn species on astrocyte function and their potential impact on the pathogenesis of Parkinson's disease and related α-synucleinopathies.
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Cover Image
Cover Image
In this issue, Keith Willison reviews of the structure and evolution of eukaryotic CCT (chaperonin-containing TCP-1) and how it effects actin folding. The cover image shows a space-fill model of the CCT3/γ apical domain with its solvent-accessible-binding surface highlighted in brown and a stretch of bound poly-Gln β-strand occupying the long stretch of anchoring sites. For further details, see pages 3009–3034. Image kindly provided by Miriam Eisenstein (Weizmann Institute for Science).
Impact of monomeric, oligomeric and fibrillar alpha-synuclein on astrocyte reactivity and toxicity to neurons
Cecilia Chavarría, Sebastián Rodríguez-Bottero, Celia Quijano, Patricia Cassina, José M. Souza; Impact of monomeric, oligomeric and fibrillar alpha-synuclein on astrocyte reactivity and toxicity to neurons. Biochem J 15 October 2018; 475 (19): 3153–3169. doi: https://doi.org/10.1042/BCJ20180297
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