| Autor: |
Naomi P. Visanji, Heather H. C. Lau, Gabor G. Kovacs, Ain Kim, Raphaella W. L. So, M. R. Luquin, Anthony E. Lang, Joel C. Watts, Ivan Martinez-Valbuena, Andrew Gao, Michael Seidman, Sohaila Alshimemeri |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.08.10.455800 |
| Popis: |
Severalin vitroandin vivofindings have consistently shown that α-synuclein derived from multiple system atrophy (MSA) subjects has more seeding capacity than Parkinson’s disease-derived α-synuclein. However, reliable detection of α-synuclein derived from MSA using seeded amplification assays, such as the Real-Time Quaking-induced Conversion, has remained challenging. Here we demonstrate that the interaction of the Thioflavin T dye with α-synuclein from MSA and Parkinson’s disease patients can be modulated by the type of salt, pH, and ionic strength used to generate strain-specific reaction buffers. Employing this novel approach, we have generated a streamlined Real-Time Quaking-induced Conversion assay capable of categorizing MSA brains according to their α-synuclein seeding behavior, and to unravel a previously unrecognized heterogeneity in seeding activity between different brain regions of a given individual that goes beyond immunohistochemical observations and provide a framework for future molecular subtyping of MSA. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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