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Renin-Angiotensin System Gene Expression And Neurodegenerative Diseases., Benjamin Goldstein, Robert Charles Speth, Malav Suchin Trivedi
Renin-Angiotensin System Gene Expression And Neurodegenerative Diseases., Benjamin Goldstein, Robert Charles Speth, Malav Suchin Trivedi
Faculty Articles
HYPOTHESIS: Single nucleotide polymorphisms and altered gene expression of components of the renin-angiotensin system (RAS) are associated with neurodegenerative diseases.
INTRODUCTION: Drugs that interact with the RAS have been shown to affect the course of neurodegenerative disease, suggesting that abnormalities in the RAS may contribute to neurodegenerative disease.
MATERIALS AND METHODS: A meta-analysis of genome-wide association studies and gene expression data for 14 RAS-related proteins was carried out for five neurodegenerative diseases: Alzheimer's disease, Parkinson's disease, narcolepsy, amyotrophic lateral sclerosis and multiple sclerosis.
RESULTS: No single nucleotide polymorphisms in any of the 14 RAS-related protein genes were significantly associated with …
An In Vitro And In Vivo Investigation Of Bivalent Ligands That Display Preferential Binding And Functional Activity For Different Melanocortin Receptor Homodimers, Cody J Lensing, Katie T Freeman, Sathya M Schnell, Danielle N Adank, Robert Charles Speth, Carrie Haskell-Luevano
An In Vitro And In Vivo Investigation Of Bivalent Ligands That Display Preferential Binding And Functional Activity For Different Melanocortin Receptor Homodimers, Cody J Lensing, Katie T Freeman, Sathya M Schnell, Danielle N Adank, Robert Charles Speth, Carrie Haskell-Luevano
Faculty Articles
Pharmacological probes for the melanocortin receptors have been utilized for studying various disease states including cancer, sexual function disorders, Alzheimer's disease, social disorders, cachexia, and obesity. This study focused on the design and synthesis of bivalent ligands to target melanocortin receptor homodimers. Lead ligands increased binding affinity by 14- to 25-fold and increased cAMP signaling potency by 3- to 5-fold compared to their monovalent counterparts. Unexpectedly, different bivalent ligands showed preferences for particular melanocortin receptor subtypes depending on the linker that connected the binding scaffolds, suggesting structural differences between the various dimer subtypes. Homobivalent compound 12 possessed a functional profile …