Cytological Profiling of Natural Product Scaffolds Libraries for Parkinson’s Disease

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Author(s)
Primary Supervisor
Wood, Stephen
Quinn, Ronald
Year published
2016
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Show full item recordAbstract
Parkinson’s disease (PD) is a highly debilitating age-related neurodegenerative disorder arising from the prominent loss of dopaminergic nigro-striatal tracts. It affects approximately 2% of the population over 65 years of age. The majority of cases of PD arise from complex interactions between a myriad of risk-associated genes and environmental risk factors. Due to the intricate combination of multiple factors, efforts towards designing therapies for PD have demonstrated limited efficacy. Current drugs mainly relieve symptoms rather than retarding or modifying disease progression. Natural products (NPs) have served as an ...
View more >Parkinson’s disease (PD) is a highly debilitating age-related neurodegenerative disorder arising from the prominent loss of dopaminergic nigro-striatal tracts. It affects approximately 2% of the population over 65 years of age. The majority of cases of PD arise from complex interactions between a myriad of risk-associated genes and environmental risk factors. Due to the intricate combination of multiple factors, efforts towards designing therapies for PD have demonstrated limited efficacy. Current drugs mainly relieve symptoms rather than retarding or modifying disease progression. Natural products (NPs) have served as an invaluable source of new drugs for over 25 years. It stands to reason therefore that these bioactive small molecules may themselves become promising therapeutic agents for PD. Cytological profiling has emerged as a powerful tool to rapidly identify the effects of thousands of small molecules on the biological properties of the cells. This platform employs an automated microscopy system from which images of cells in multi well plate format are obtained. Subsequently the resulting images are segmented and a number of cytological features are quantified based on the amount and location of fluorescence within cells. Together with effective downstream data processing, image-based screening technologies play crucial roles in drug lead discovery and optimization. Notably, among 75 first-in-class small molecule drugs approved by US Food and Drug Administration between 1999 and 2008, 28 were discovered by phenotypic screening.
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View more >Parkinson’s disease (PD) is a highly debilitating age-related neurodegenerative disorder arising from the prominent loss of dopaminergic nigro-striatal tracts. It affects approximately 2% of the population over 65 years of age. The majority of cases of PD arise from complex interactions between a myriad of risk-associated genes and environmental risk factors. Due to the intricate combination of multiple factors, efforts towards designing therapies for PD have demonstrated limited efficacy. Current drugs mainly relieve symptoms rather than retarding or modifying disease progression. Natural products (NPs) have served as an invaluable source of new drugs for over 25 years. It stands to reason therefore that these bioactive small molecules may themselves become promising therapeutic agents for PD. Cytological profiling has emerged as a powerful tool to rapidly identify the effects of thousands of small molecules on the biological properties of the cells. This platform employs an automated microscopy system from which images of cells in multi well plate format are obtained. Subsequently the resulting images are segmented and a number of cytological features are quantified based on the amount and location of fluorescence within cells. Together with effective downstream data processing, image-based screening technologies play crucial roles in drug lead discovery and optimization. Notably, among 75 first-in-class small molecule drugs approved by US Food and Drug Administration between 1999 and 2008, 28 were discovered by phenotypic screening.
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Thesis Type
Thesis (Masters)
Degree Program
Master of Philosophy (MPhil)
School
School of Natural Sciences
Copyright Statement
The author owns the copyright in this thesis, unless stated otherwise.
Item Access Status
Public
Subject
Parkinson’s disease (PD)
Cytological profiling
Neurodegenerative disorder
Natural products
Phenotypic screening