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In vitro models of multiple system atrophy



α-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 α-synuclein aggregation in oligodendroglial cells is still obscure, in particular, whether α-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 α-synuclein in glial cell cultures. With this simplified system, we have demonstrated that α-synuclein significantly affects the survival of glia and its vulnerability to environmental stress, which might represent a major step in the pathogenesis of MSA. © 2005 Movement Disorder Society