Age-dependent defects of alpha-synuclein oligomer uptake in microglia and monocytes
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- 作者：Corinna Bliederhaeuser ; Veselin Grozdanov ; Anna Speidel…
- 关键词：Microglia ; Monocytes ; Alpha ; synuclein ; Parkinson’s disease ; Exosomes ; Aging
- 刊名：Acta Neuropathologica
- 出版年：2016
- 出版时间：March 2016
- 年：2016
- 卷：131
- 期：3
- 页码：379-391
- 全文大小：1,100 KB
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Veselin Grozdanov (1)
Anna Speidel (2)
Lisa Zondler (1)
Wolfgang P. Ruf (1)
Hanna Bayer (1)
Martin Kiechle (1)
Marisa S. Feiler (1)
Axel Freischmidt (1)
David Brenner (1)
Anke Witting (1)
Bastian Hengerer (2)
Marcus Fändrich (3)
Albert C. Ludolph (1)
Jochen H. Weishaupt (1)
Frank Gillardon (2)
Karin M. Danzer (1)
1. Department of Neurology, Ulm University, Albert Einstein Allee 11, 89081, Ulm, Germany
2. Boehringer Ingelheim Pharma GmbH and Co KG, CNS Diseases Research, Biberach Riss, Germany
3. Institute for Pharmaceutical Biotechnology, Center for Biomedical Research, University of Ulm, Ulm, Germany - 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Pathology - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-0533
文摘
Extracellular alpha-synuclein (αsyn) oligomers, associated to exosomes or free, play an important role in the pathogenesis of Parkinson’s disease (PD). Increasing evidence suggests that these extracellular moieties activate microglia leading to enhanced neuronal damage. Despite extensive efforts on studying neuroinflammation in PD, little is known about the impact of age on microglial activation and phagocytosis, especially of extracellular αsyn oligomers. Here, we show that microglia isolated from adult mice, in contrast to microglia from young mice, display phagocytosis deficits of free and exosome-associated αsyn oligomers combined with enhanced TNFα secretion. In addition, we describe a dysregulation of monocyte subpopulations with age in mice and humans. Accordingly, human monocytes from elderly donors also show reduced phagocytic activity of extracellular αsyn. These findings suggest that these age-related alterations may contribute to an increased susceptibility to pathogens or abnormally folded proteins with age in neurodegenerative diseases. Keywords Microglia Monocytes Alpha-synuclein Parkinson’s disease Exosomes Aging