?-Synuclein impairs oligodendrocyte progenitor maturation in multiple system atrophy

May VEL, Ettle B, Pöhler AM, Nuber S, Ubhi K, Rockenstein E, Winner B, Wegner M, Masliah E, Winkler J (2014)

Publication Type: Journal article

Publication year: 2014


Publisher: Elsevier

Book Volume: 35

Pages Range: 2357-68

Journal Issue: 10

DOI: 10.1016/j.neurobiolaging.2014.02.028


Multiple system atrophy (MSA), an atypical parkinsonian disorder, is characterized by ?-synuclein (?-syn(+)) cytoplasmatic inclusions in mature oligodendrocytes. Oligodendrocyte progenitor cells (OPCs) represent a distinct cell population with the potential to replace dysfunctional oligodendrocytes. However, the role of OPCs in MSA and their potential to replace mature oligodendrocytes is still unclear. A postmortem analysis in MSA patients revealed ?-syn within OPCs and an increased number of striatal OPCs. In an MSA mouse model, an age-dependent increase of dividing OPCs within the striatum and the cortex was detected. Despite of myelin loss, there was no reduction of mature oligodendrocytes in the corpus callosum or the striatum. Dissecting the underlying molecular mechanisms an oligodendroglial cell line expressing human ?-syn revealed that ?-syn delays OPC maturation by severely downregulating myelin-gene regulatory factor and myelin basic protein. Brain-derived neurotrophic factor was reduced in MSA models and its in vitro supplementation partially restored the phenotype. Taken together, efficacious induction of OPC maturation may open the window to restore glial and neuronal function in MSA.

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May, V.E.L., Ettle, B., Pöhler, A.-M., Nuber, S., Ubhi, K., Rockenstein, E.,... Winkler, J. (2014). ?-Synuclein impairs oligodendrocyte progenitor maturation in multiple system atrophy. Neurobiology of Aging, 35(10), 2357-68. https://doi.org/10.1016/j.neurobiolaging.2014.02.028


May, Verena Elisabeth Luise, et al. "?-Synuclein impairs oligodendrocyte progenitor maturation in multiple system atrophy." Neurobiology of Aging 35.10 (2014): 2357-68.

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