α-Synuclein impairs oligodendrocyte progenitor maturation in multiple system atrophy

May, Verena E.L.; Ettle, Benjamin; Poehler, Anne-Maria; Nuber, Silke; Ubhi, Kiren; Rockenstein, Edward; Winner, Beate; Wegner, Michael; Masliah, Eliezer; Winkler, Jürgen

doi:10.1016/j.neurobiolaging.2014.02.028

Cited by 64 publications

(97 citation statements)

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“…Similar results have been obtained by Ahmed and colleagues analyzing cerebellar white matter of MSA patients [18] . In line with these observations, we detected increased numbers of proliferative OPCs in transgenic mice expressing aSyn under the control of the OLG specific myelin basic protein (MBP)-promoter (MBP::aSyn) [1] . This transgenic mouse line represents a pre-clinical MSA model showing a profound myelination deficit accompanied by a severe motor phenotype [8] .…”

Section: Research Highlightsupporting

confidence: 75%

“…Intriguingly, we observed increased numbers of striatal platelet-derived growth factor receptor-alpha (PDGFRa)-positive OPCs in MSA patients suggesting a proliferative reaction of OPCs in response to demyelination in MSA [1] . Similar results have been obtained by Ahmed and colleagues analyzing cerebellar white matter of MSA patients [18] .…”

Section: Research Highlightmentioning

confidence: 80%

“…Thus, we analyzed OPCs post-mortem in MSA brains and in a pre-clinical MSA mouse model expressing aSyn under the myelin basic protein (MBP) promoter. Importantly, we detected elevated numbers of striatal OPCs in MSA and its model [1] . Observing aSyn-positive OPCs in MSA patients, we additionally established two independent in vitro models in order to explore the effect of intracellular aSyn on OPC maturation.…”

mentioning

confidence: 76%

“…We recently addressed the role of OPCs in MSA by investigating human post-mortem tissue as well as pre-clinical animal and cell culture models for MSA [1,2] . Intriguingly, we observed increased numbers of striatal platelet-derived growth factor receptor-alpha (PDGFRa)-positive OPCs in MSA patients suggesting a proliferative reaction of OPCs in response to demyelination in MSA [1] .…”

Section: Research Highlightmentioning

confidence: 99%

“…Observing aSyn-positive OPCs in MSA patients, we additionally established two independent in vitro models in order to explore the effect of intracellular aSyn on OPC maturation. Both stable aSyn expressing OPC-like central glia-4 (CG4) cells [1] and transiently aSyn expressing primary OPCs derived from neonatal rats [2] robustly showed a severely reduced maturation. Similarly, primary OPCs exhibit a delayed maturation upon uptake of recombinant aSyn [2] .…”

mentioning

confidence: 99%

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Promoting oligodendrocyte progenitor cell maturation and remyelination as a novel therapeutical approach for multiple system atrophy

Ettle

Schlachetzki

2015

Ther Targets Neurol Dis

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Alpha-synuclein (aSyn) aggregation within mature oligodendrocytes is the characteristic neuropathological feature of multiple system atrophy (MSA). In fact, dysfunction of oligodendrocytes is considered as a primary event in MSA pathogenesis leading to myelin loss and, ultimately, reduced axonal integrity and neuronal cell loss. Oligodendrocyte progenitor cells (OPCs) are widely distributed in the adult central nervous system and represent a potential endogenous source for replacement of such dysfunctional oligodendrocytes. The extent to which OPCs are affected in MSA or even contribute to MSA pathogenesis remains undefined. Thus, we analyzed OPCs post-mortem in MSA brains and in a pre-clinical MSA mouse model expressing aSyn under the myelin basic protein (MBP) promoter. Importantly, we detected elevated numbers of striatal OPCs in MSA and its model [1] . Observing aSyn-positive OPCs in MSA patients, we additionally established two independent in vitro models in order to explore the effect of intracellular aSyn on OPC maturation. Both stable aSyn expressing OPC-like central glia-4 (CG4) cells [1] and transiently aSyn expressing primary OPCs derived from neonatal rats [2] robustly showed a severely reduced maturation. Similarly, primary OPCs exhibit a delayed maturation upon uptake of recombinant aSyn [2] . Taken together, our findings indicate that OPC dysfunction is a pathological feature of MSA. In addition, promoting OPC differentiation may represent a novel and promising interventional strategy for therapeutic approaches in MSA.

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Section: Research Highlightsupporting

confidence: 75%

Section: Research Highlightmentioning

confidence: 80%

mentioning

confidence: 76%

Section: Research Highlightmentioning

confidence: 99%

mentioning

confidence: 99%

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Promoting oligodendrocyte progenitor cell maturation and remyelination as a novel therapeutical approach for multiple system atrophy

Ettle

Schlachetzki

2015

Ther Targets Neurol Dis

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Multiple System Atrophy: Recent Developments and Future Perspectives

et al. 2019

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Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disorder characterized by a variable combination of parkinsonism, cerebellar impairment, and autonomic dysfunction. The pathologic hallmark is the accumulation of aggregated α‐synuclein in oligodendrocytes, forming glial cytoplasmic inclusions, which qualifies MSA as a synucleinopathy together with Parkinson's disease and dementia with Lewy bodies. The underlying pathogenesis is still not well understood. Some symptomatic treatments are available, whereas neuroprotection remains an urgent unmet treatment need. In this review, we critically appraise significant developments of the past decade with emphasis on pathogenesis, diagnosis, prognosis, and treatment development. We further discuss unsolved questions and highlight some perspectives. © 2019 International Parkinson and Movement Disorder Society

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Glial Cells as Key Orchestrators of Neural Degeneration in Basal Ganglia Disorders

Bhaduri

Alladi

2022

The Biology of Glial Cells: Recent Advances

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α-Synuclein impairs oligodendrocyte progenitor maturation in multiple system atrophy

Cited by 64 publications

References 57 publications

Promoting oligodendrocyte progenitor cell maturation and remyelination as a novel therapeutical approach for multiple system atrophy

Promoting oligodendrocyte progenitor cell maturation and remyelination as a novel therapeutical approach for multiple system atrophy

Multiple System Atrophy: Recent Developments and Future Perspectives

Glial Cells as Key Orchestrators of Neural Degeneration in Basal Ganglia Disorders

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