Robust Central Nervous System Pathology in Transgenic Mice Following Peripheral Injection of α-Synuclein Fibrils

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2016 Nov 18

PMID 27852849

Citations 53

Authors

Jacob I Ayers

Mieu M Brooks

Nicola J Rutherford

Jasie K Howard

Zachary A Sorrentino

Cara J Riffe

Benoit I Giasson

Affiliations

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Abstract

Importance: The misfolding and accumulation of α-synuclein (αS) inclusions are found in a number of neurodegenerative disorders and is a hallmark feature of Parkinson's disease (PD) and PD-related diseases. Similar characteristics have been observed between the infectious prion protein and αS, including its ability to spread from the peripheral nervous system and along neuroanatomical tracts within the central nervous system. In this study, we extend our previous results and investigate the efficiency of intravenous (i.v.), intraperitoneal (i.p.), and intramuscular (i.m.) routes of injection of αS fibrils and other protein controls. Our data reveal that injection of αS fibrils via these peripheral routes in αS-overexpressing mice are capable of inducing a robust αS pathology and in some cases cause paralysis. Furthermore, soluble, nonaggregated αS also induced αS pathology, albeit with much less efficiency. These findings further support and extend the idea of αS neuroinvasion from peripheral exposures.

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