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Glial cell death induced by overexpression of α‐synuclein
Author(s) -
Stefanova Nadia,
Klimaschewski Lars,
Poewe Werner,
Wenning Gregor K.,
Reindl Markus
Publication year - 2001
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.1171
Subject(s) - alpha synuclein , programmed cell death , biology , microbiology and biotechnology , synucleinopathies , cytoplasmic inclusion , astrocyte , dementia with lewy bodies , autophagy , pathology , apoptosis , neuroscience , cytoplasm , parkinson's disease , medicine , dementia , central nervous system , disease , biochemistry
α‐Synuclein is present in intracellular protein aggregates that are hallmarks of common neurodegenerative disorders including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. α‐Synuclein is localized in neurons and presynaptic terminals. Under pathological conditions, however, it is also found in glia. The role of α‐synuclein in glial cells and its relevance to the molecular pathology of neurodegenerative diseases is presently unclear. To investigate the consequence of α‐synuclein overexpression in glia, we transfected U373 astrocytoma cells with vectors encoding wild‐type human α‐synuclein or C‐terminally truncated synuclein fused to red fluorescent protein. α‐synuclein immunocytochemistry of transfected astroglial cells revealed diffuse cytoplasmic labeling associated with discrete inclusions both within cell bodies and processes. Susceptibility to oxidative stress was increased in astroglial cells overexpressing α‐synuclein, particularly in the presence of cytoplasmic inclusions. Furthermore, overexpression of α‐synuclein induced apoptotic death of astroglial cells as shown by TUNEL staining. Our in vitro model is the first to replicate salient features of the glial pathology associated with α‐synucleinopathies. It provides a simple testbed to further explore the cascade of events that leads to apoptotic glial cell death in some of these disorders; it may also be useful to assess the effects of therapeutic interventions including antioxidative and antiapoptotic strategies. J. Neurosci. Res. 65:432–438, 2001. © 2001 Wiley‐Liss, Inc.