The role of alpha-synuclein in the pathogenesis of multiple system atrophy.
The discovery of glial cytoplasmic inclusions (GCIs) in 1989 helped to define multiple system atrophy (MSA) as a clinicopathological entity, and drew attention to the prominent role played by these inclusions in the pathogenesis of the disorder. Subsequently, GCIs were shown to be highly positive for alpha-synuclein, a neuronal protein that is normally absent in oligodendroglia except during embryonic development. The source of oligodendroglial alpha-synuclein aggregation in MSA is unknown. Since genetic overexpression has been excluded, active uptake from dying neurons remains a possibility. The similar topography of oligodendroglial and neuronal pathology in MSA suggests a fundamental disturbance of the functional unit between oligodendroglia, axon, and neuron. Transgenic MSA mouse models are now available to determine these aspects of cellular disturbance experimentally.
Wenning
Gregor K
GK
Department of Neurology, University of Innsbruck, School of Medicine, Anichstrasse 35, 6020, Innsbruck, Austria.
Jellinger
Kurt A
KA
D000818:Animals; D030801:Animals, Genetically Modified / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D008959:Models, Neurological; D019578:Multiple System Atrophy / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D051843:Synucleins; D051844:alpha-Synuclein
D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein