Meszaros L, Himmler M, Schneider Y, Arnold P, Dörje F, Schubert DW, Winkler J (2023)
Publication Language: English
Publication Type: Journal article
Publication year: 2023
Book Volume: 59
Pages Range: 308-315
Journal Issue: 2
DOI: 10.1111/ejn.16215
Multiple system atrophy (MSA) is a rare and rapidly progressive atypical parkinsonian disorder characterized by oligodendroglial cytoplasmic inclusions containing α-synuclein (α-syn), demyelination, inflammation and neuronal loss. To date, no disease-modifying therapy is available. Targeting α-syn-driven oligodendroglial dysfunction and demyelination presents a potential therapeutic approach for restricting axonal dysfunction, neuronal loss and disease progression. The present study investigated the promyelinogenic potential of sobetirome, a blood–brain barrier permeable and central nervous system selective thyromimetic in the context of an in vitro MSA model. Oligodendrocyte precursor cells (OPCs) were obtained from transgenic mice overexpressing human α-syn specifically in oligodendrocytes (MBP29 mouse line), a well-described MSA model, and non-transgenic littermates. mRNA and protein expression analyses revealed a substantial rescue effect of sobetirome on myelin-specific proteins in control and α-syn overexpressing oligodendrocytes. Furthermore, myelination analysis using nanofibres confirmed that sobetirome increases both the length and number of myelinated segments per oligodendrocyte in primary murine α-syn overexpressing oligodendrocytes and their respective control. These results suggest that sobetirome may be a promising thyromimetic compound targeting an important neuropathological hallmark of MSA.
APA:
Meszaros, L., Himmler, M., Schneider, Y., Arnold, P., Dörje, F., Schubert, D.W., & Winkler, J. (2023). Sobetirome rescues α-synuclein-mediated demyelination in an in vitro model of multiple system atrophy. European Journal of Neuroscience, 59(2), 308-315. https://dx.doi.org/10.1111/ejn.16215
MLA:
Meszaros, Lisa, et al. "Sobetirome rescues α-synuclein-mediated demyelination in an in vitro model of multiple system atrophy." European Journal of Neuroscience 59.2 (2023): 308-315.
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