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

Biochemical and Biophysical Research Communications Elsevier

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.

Authors with CRIS profile

Alana Hoffmann Professur für Molekulare Neurologie Benjamin Ettle Professur für Molekulare Neurologie Ariane Bruno Lehrstuhl für Biochemie und Molekulare Medizin Anna-Carin Hoffmann Interdisziplinäres Zentrum für Klinische Forschung IZKF-Förderlinien Julia von Wittgenstein Professur für Molekulare Medizin mit dem Schwerpunkt Molekulare Bildgebung Jürgen Winkler Professur für Molekulare Neurologie Wei Xiang Lehrstuhl für Biochemie und Molekulare Medizin Johannes Schlachetzki Department of Molecular Neurology

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

University of California, Riverside (UCR) US United States (USA) (US)

How to cite

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://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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