Glial dysfunction in the pathogenesis of a-synucleinopathies: emerging concepts
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Lisa Fellner Kurt A. Jellinger Gregor K. Wenning Nadia Stefanova
- چاپ و سال / کشور: 2011
Description
Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) are adult onset neurodegenerative disorders characterised by prominent intracellular a-synuclein aggregates (a-synucleinopathies). The glial contribution to neurodegeneration in a-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 a-synuclein aggregates.Accumulating experimental evidence in PDmodels suggests that astrogliosis andmicrogliosis 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 a-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 a-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 a-synucleinopathies as well as current pitfalls for disease-modification in clinical trials are discussed.
Acta Neuropathol (2011) 121:675–693 DOI 10.1007/s00401-011-0833- Received: 8 April 2011 / Revised: 4 May 2011 / Accepted: 4 May 2011 / Published online: 12 May 2011
