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Pharmacology

Graduate Theses and Dissertations

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Compensatory Mechanisms Of Neuroprotection By Pkd Signaling Against Oxidative Damage In Experimental Models Of Parkinson's Disease (Pd): Relevance To Pd Drug Discovery Strategies, Arunkumar Asaithambi Jan 2011

Compensatory Mechanisms Of Neuroprotection By Pkd Signaling Against Oxidative Damage In Experimental Models Of Parkinson's Disease (Pd): Relevance To Pd Drug Discovery Strategies, Arunkumar Asaithambi

Graduate Theses and Dissertations

Oxidative stress is a key pathophysiological mechanism contributing to the selective degeneration of dopaminergic neurons in Parkinson's disease. Unraveling the molecular mechanisms underlying various stages of oxidative neuronal damage is critical to better understanding the diseases and developing new treatment modalities. In this study, we identified that protein kinase D1 (PKD1) functions as a key anti-apoptotic kinase to protect neuronal cells against early stages of oxidative stress. Blockade of PKCδ cleavage, PKCδ knockdown or overexpression of a cleavage-resistant PKCδ mutant effectively attenuated PKD1 activation, indicating that PKCδ proteolytic activation regulates PKD1 phosphorylation. We also identified that phosphorylation of S916 ...