Preformed fibrils generated from mouse alpha-synuclein produce more inclusion pathology in rats than fibrils generated from rat alpha-synuclein.

Autor: Howe JW; Department of Translational Neuroscience, Michigan State University, Grand Rapids, MI, USA; Neuroscience Program, Michigan State University, East Lansing, MI, USA., Sortwell CE; Department of Translational Neuroscience, Michigan State University, Grand Rapids, MI, USA; Neuroscience Program, Michigan State University, East Lansing, MI, USA; Mercy Health Hauenstein Neuroscience Medical Center, Grand Rapids, MI, USA., Duffy MF; Department of Translational Neuroscience, Michigan State University, Grand Rapids, MI, USA; Neuroscience Program, Michigan State University, East Lansing, MI, USA., Kemp CJ; Department of Translational Neuroscience, Michigan State University, Grand Rapids, MI, USA., Russell CP; Cell and Molecular Biology Department, Grand Valley State University, Allendale, MI, USA., Kubik M; Department of Translational Neuroscience, Michigan State University, Grand Rapids, MI, USA., Patel P; Cell and Molecular Biology Department, Grand Valley State University, Allendale, MI, USA., Luk KC; Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., El-Agnaf OMA; Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, Qatar., Patterson JR; Department of Translational Neuroscience, Michigan State University, Grand Rapids, MI, USA. Electronic address: Joseph.Patterson@hc.msu.edu.
Jazyk: angličtina
Zdroj: Parkinsonism & related disorders [Parkinsonism Relat Disord] 2021 Aug; Vol. 89, pp. 41-47. Date of Electronic Publication: 2021 Jun 19.
DOI: 10.1016/j.parkreldis.2021.06.010
Abstrakt: Background: Alpha-synuclein (α-syn) preformed fibril (PFF)-induced pathology can be used to study the features and progression of synucleinopathies, such as Parkinson's disease. Intrastriatal injection of mouse α-syn PFFs produce accumulation of α-syn pathology in both mice and rats. Previous studies in mice have revealed that greater sequence homology between the α-syn amino acid sequence used to produce PFFs with that of the endogenous host α-syn increases α-syn pathology in vivo.
New Methods: Based on the prediction that greater sequence homology will result in more α-syn pathology, PFFs generated from recombinant rat α-syn (rPFFs) were used instead of PFFs produced from recombinant mouse α-syn (mPFFs), which are normally used in the model. Rats received unilateral intrastriatal injections of either rPFFs or mPFFs and accumulation of α-syn phosphorylated at serine 129 (pSyn) was examined at 1-month post-surgery.
Results: Rats injected with mPFFs exhibited abundant accumulation of α-syn inclusions in the substantia nigra and cortical regions, whereas in rats injected with rPFFs had significantly fewer SNpc neurons containing pSyn inclusions (≈60% fewer) and little, if any, pSyn inclusions were observed in the cortex.
Conclusions: Our results suggest that additional factors beyond the degree of sequence homology between host α-syn and injected recombinant α-syn impact efficiency of seeding and subsequent inclusion formation. More practically, these findings caution against the use of rPFFs in the rat preformed fibril model.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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