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Articles 1 - 2 of 2
Full-Text Articles in Chemicals and Drugs
Novel Therapeutic Approaches For Juvenile Neuronal Ceroid Lipofuscinosis (Cln3), Megan Elizabeth Bosch
Novel Therapeutic Approaches For Juvenile Neuronal Ceroid Lipofuscinosis (Cln3), Megan Elizabeth Bosch
Theses & Dissertations
Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by autosomal recessive mutations in CLN3. Neuronal loss is thought to occur via glutamate excitotoxicity; however, little is known about neuron-astrocyte glutamate regulation in JNCL. We discovered that Cln3Δex7/8 astrocytes have significantly lower basal spontaneous Ca2+ oscillations and decreased responses to glutamate, indicating a disrupted signaling network. Cln3Δex7/8 astrocytes also displayed significantly lower basal mitochondrial respiration and ATP production, suggesting impaired metabolic functions. Concurrent with diminished astrocyte metabolism and Ca2+ signaling, Cln3Δex7/8 neurons were hyper-responsive to glutamate stimulation. These studies suggest that CLN3 …
Novel Therapeutic Strategies For Treatment Of Castration-Resistant Prostate Cancer, Matthew A. Ingersoll
Novel Therapeutic Strategies For Treatment Of Castration-Resistant Prostate Cancer, Matthew A. Ingersoll
Theses & Dissertations
Prostate cancer (PCa) remains the most commonly diagnosed solid tumor and is the third leading cause of cancer-related death in United States men. While androgen deprivation therapy is the current standard-of-care treatment for metastatic PCa, most patients eventually relapse and develop castration-resistant (CR) tumors, for which there is currently no effective treatment. Therefore, synthesis of novel therapeutic agents and identification of alternative target proteins are necessary to improve treatment. Herein, I investigate the efficacy of novel imidazopyridine and statin derivatives as alternative therapeutic compounds. These molecules not only inhibit androgen receptor signaling, but also block activation of the AKT axis, …