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Glial cell death induced by overexpression of α‐synuclein

Identifieur interne : 001A61 ( Main/Exploration ); précédent : 001A60; suivant : 001A62

Glial cell death induced by overexpression of α‐synuclein

Auteurs : Nadia Stefanova [Autriche, Bulgarie] ; Lars Klimaschewski [Autriche] ; Werner Poewe [Autriche] ; Gregor K. Wenning [Autriche] ; Markus Reindl [Autriche]

Source :

RBID : ISTEX:93685E9138CCBF6824755999FAF57F488E8F92F5

English descriptors

Abstract

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.

Url:
DOI: 10.1002/jnr.1171


Affiliations:


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<div type="abstract" xml:lang="en">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.</div>
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