Date of Award

2021

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Pharmacology

First Advisor

Robert H. Mach

Abstract

Poly (ADP-ribose)-polymerase 1 (PARP-1) is a DNA repair enzyme that has been implicated in regulating a number of inflammatory processes. Hyperactivation of PARP-1 has been linked to a number of inflammation-associated clinical conditions, including cancer, metabolic disorders, and neurodegenerative disease. Parkinson’s disease (PD) is a complex neurodegenerative disorder characterized by bradykinesia, tremors, and rigidity. PD is the second most common neurodegenerative disease after Alzheimer’s disease, with an incidence rate that is estimated to increase by more than 30% in the next decade. Our understanding on the progression and mechanisms underlying the onset of PD have grown enormously in the past few decades. There is now growing evidence suggesting that PARP-1 hyperactivation is involved in driving PD and that poly (ADP-ribose) (PAR) - dependent cell death is responsible for neuronal loss. While inhibition of PARP-1 activity has proven beneficial in cancer therapy, there is a need to design and validate PARP-1 inhibitors (PARPi) with optimal physicochemical properties for complex neurological conditions. These pharmacological interventions may provide an alternative therapeutic approach for managing PD.

Embargoed

Available to all on Saturday, May 11, 2024

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