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Acta Neuropathologica
Published in: Acta Neuropathologica 6/2011

01-06-2011 | Review

Glial dysfunction in the pathogenesis of α-synucleinopathies: emerging concepts

Authors: Lisa Fellner, Kurt A. Jellinger, Gregor K. Wenning, Nadia Stefanova

Published in: Acta Neuropathologica | Issue 6/2011

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Abstract

Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) are adult onset neurodegenerative disorders characterised by prominent intracellular α-synuclein aggregates (α-synucleinopathies). The glial contribution to neurodegeneration in α-synucleinopathies was largely underestimated until recently. However, brains of PD and DLB patients exhibit not only neuronal inclusions such as Lewy bodies or Lewy neurites but also glial α-synuclein aggregates. Accumulating experimental evidence in PD models suggests that astrogliosis and microgliosis act as important mediators of neurodegeneration playing a pivotal role in both disease initiation and progression. In MSA, oligodendrocytes are intriguingly affected by aberrant cytoplasmic accumulation of α-synuclein (glial cytoplasmic inclusions, Papp-Lantos bodies). Converging evidence from human postmortem studies and transgenic MSA models suggests that oligodendroglial dysfunction both triggers and exacerbates neuronal degeneration. This review summarises the wide range of responsibilities of astroglia, microglia and oligodendroglia in the healthy brain and the changes in glial function associated with ageing. We then provide a critical analysis of the role of glia in α-synucleinopathies including putative mechanisms promoting a chronically diseased glial microenvironment which can lead to detrimental neuronal changes, including cell loss. Finally, major therapeutic strategies targeting glial pathology in α-synucleinopathies as well as current pitfalls for disease-modification in clinical trials are discussed.
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Metadata
Title
Glial dysfunction in the pathogenesis of α-synucleinopathies: emerging concepts
Authors
Lisa Fellner
Kurt A. Jellinger
Gregor K. Wenning
Nadia Stefanova
Publication date
01-06-2011
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 6/2011
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-011-0833-z

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