In vitro models of multiple system atrophy.
alpha-Synuclein represents the major constituent of oligodendroglial cytoplasmic inclusions, the hallmark lesion of multiple system atrophy (MSA), a progressive disorder that is associated with selective degenerative cell loss in basal ganglia, cerebellum, brainstem, and spinal cord. The role of abnormal alpha-synuclein aggregation in oligodendroglial cells is still obscure, in particular, whether alpha-synuclein might impair oligodendroglial and, secondarily, neuronal integrity of those cells in the diseased brain. In an attempt to answer some of these questions, we have developed an "in vitro model of MSA" by expressing the wild-type or C-terminally truncated form of alpha-synuclein in glial cell cultures. With this simplified system, we have demonstrated that alpha-synuclein significantly affects the survival of glia and its vulnerability to environmental stress, which might represent a major step in the pathogenesis of MSA.
Stefanova
Nadia
N
Neurological Research Laboratory, Department of Neurology, University Hospital of Innsbruck, Austria. nadia.stefanova@uibk.ac.at
Reindl
Markus
M
Poewe
Werner
W
Wenning
Gregor K
GK
D001479:Basal Ganglia / Q000378:metabolism / Q000473:pathology; D001933:Brain Stem / Q000378:metabolism / Q000473:pathology; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D004777:Environment; D006801:Humans; D066298:In Vitro Techniques; D017628:Microglia / Q000378:metabolism; D019578:Multiple System Atrophy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D051844:alpha-Synuclein