Alpha-synuclein activates BV2 microglia dependent on its aggregation state

Hoffmann A, Ettle B, Bruno A, Kulinich A, Hoffmann AC, von Wittgenstein J, Winkler J, Xiang W, Schlachetzki J (2016)


Publication Type: Journal article

Publication year: 2016

Journal

Publisher: Elsevier

Book Volume: 479

Pages Range: 881-886

Journal Issue: 4

DOI: 10.1016/j.bbrc.2016.09.109

Abstract

Synucleinopathies such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are defined by the presence of intracellular alpha-synuclein aggregates in neurons and/or oligodendrocytes. In addition, post mortem tissue analysis revealed profound changes in microglial morphology, indicating microglial activation and neuroinflammation. Thus, alpha-synuclein may directly activate microglia, leading to increased production of key pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-?) and interleukin-1beta (IL-1?), which in turn modulates the disease progression. The distinct alpha-synuclein species, which mediates the activation of microglia, is not well defined. We hypothesized that microglial activation depends on a specific aggregation state of alpha-synuclein. Here, we show that primarily human fibrillar alpha-synuclein increased the production and secretion of pro-inflammatory cytokines by microglial BV2 cells compared to monomeric and oligomeric alpha-synuclein. BV2 cells also preferentially phagocytosed fibrillar alpha-synuclein compared to alpha-synuclein monomers and oligomers. Microglial uptake of alpha-synuclein fibrils and the consequent activation were time- and concentration-dependent. Moreover, the degree of fibrillization determined the efficiency of microglial internalization. Taken together, our study highlights the specific crosstalk of distinct alpha-synuclein species with microglial cells.

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APA:

Hoffmann, A., Ettle, B., Bruno, A., Kulinich, A., Hoffmann, A.-C., von Wittgenstein, J.,... Schlachetzki, J. (2016). Alpha-synuclein activates BV2 microglia dependent on its aggregation state. Biochemical and Biophysical Research Communications, 479(4), 881-886. https://dx.doi.org/10.1016/j.bbrc.2016.09.109

MLA:

Hoffmann, Alana, et al. "Alpha-synuclein activates BV2 microglia dependent on its aggregation state." Biochemical and Biophysical Research Communications 479.4 (2016): 881-886.

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