The Effect of Scyllo-inositol on the Neurodegeneration Induced by Alpha-synuclein Fibril Transmission in Mice
Year: 2015
Type: dissertation
Abstract: Recent literature suggests that inoculation of non-transgenic and transgenic mice with synthetic alpha-synuclein preformed fibrils can seed the formation of Parkinson-like pathology, implicating aggregation of alpha-synuclein in the pathogenesis of Parkinson's disease. The therapeutic scyllo-inositol, an established amyloid inhibitor, was tested to determine potential inhibitory effects on alpha-synuclein aggregation. In vitro experiments were used to establish inhibitor efficacy and demonstrated that scyllo-inositol prevented the aggregation of alpha-synuclein at multiple concentrations. To generate alpha-synuclein seeds for further in vitro and in vivo studies, alpha-synuclein fibres were sonicated as previously described. The seeds demonstrated potent acceleration of monomeric alpha-synuclein aggregation in vitro and thus were injected into the striata of two mouse models to seed pathology. Injected seeds did not demonstrate additional pathology in either model, in vivo. Altogether, scyllo-inositol interacts with alpha-synuclein demonstrating anti-aggregation effects in vitro and may function as a potential therapeutic in vivo will require further investigation.
Source: TSpace (University of Toronto)
Author: Tarek Ibrahim
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2999683983