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Title: Amyloid disease : are the oligomeric species a good therapeutic target?
Author: Irvine, Amy
ISNI:       0000 0004 7226 8532
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2018
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It is believed that in many amyloid diseases, including Alzheimer's, the primary toxic species responsible for neurodegeneration are small oligomers of the causative protein, rather than the fibres that often define the disease. Oligomers of our model protein cystatin B have, therefore, been prepared in order to characterise them. Conversion of these oligomers into non-toxic aggregates could be a good therapeutic strategy. I have, therefore, been looking at agents that facilitate oligomer detoxification as this therapeutic approach would address the underlying mechanism of disease, not just alleviate the symptoms. One example is the sage plant, Salvia sclareoides. Salvia species have been used in folk medicine as a treatment for memory loss and insomnia, as well as an antiseptic. Extracts from S. sclareoides (partitioned according to their hydrophobicity) can stop amyloid formation by converting amyloidogenic forms of cystatin B, a-synuclein and Amyloid β into non-amyloidogenic aggregates. However, compounds within the Salvia extracts do not stabilise soluble oligomeric forms of these proteins directly. The extracts remodel amyloid fibrils into amorphous aggregates. The extracts are also effective in Creutzfeld-Jakob Disease, where they reduce levels of infectious PrPSc in scrapie-infected mouse neuronal cells. The extracts, themselves, show no toxicity towards human neuronal cells.
Supervisor: Staniforth, Rosemary Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available