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Title: Alternating-lever-cyclic-ratio schedule analysis of oligomeric peptide effects on behaviour and putative pharmacotherapeutic interventions
Author: Barbour, Bridgeen
ISNI:       0000 0004 5372 5611
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2014
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Alzheimer's disease and Parkinson's disease dementia syndrome are progressive brain disorders which lead to dementia. Attempts to develop disease-modifying therapies have been frustrated by an incomplete understanding of the pathogenesis of these debilitating disorders. In Alzheimer's disease cognitive deficits may be explained by oligomeric amyloid-β that initiate a cascade of events that culminates in dementia. In Parkinson's disease dementia syndrome the aggregation of α-synuclein into oligomers is considered the disease-causative toxic mechanism in the disorder. The work reported in this thesis employed animal models of learning and memory to evaluate the therapeutic efficacy of putative small therapeutic molecule compounds in the alleviation of behavioural symptoms related to Alzheimer's disease and Parkinson's disease dementia syndrome. The emphasis on small molecule compounds was deliberate, as these are the most likely to be orally bioavailable and blood-brain barrier penetrable. The experimental results showed that oligomeric amyloid-β is associated with the cognitive deficits found in Alzheimer's disease. Similarly, the formation of α-synuclein into oligomers appears to be the disease-causative toxic mechanism in Parkinson's disease dementia syndrome. The major finding in this thesis is that pharmacological targeting of these toxic oligomeric mechanisms may protect against the onset or slow the progression of Alzheimer's disease and Parkinson's disease dementia syndrome.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available