Presenter Information

Jade BosicFollow

Presentation Type

Presentation

Abstract

More than 5 million Americans are living with Alzheimer’s Disease (AD) and an American develops AD every 68 seconds. With no cures or significantly effective treatments available the number of Americans with AD is estimated to reach 7.1 million in 2025. AD is characterized by the increase in beta-amyloid plaques located in the extracellular space between the brain’s nerve cells. The endogenous chemical, retinoic acid (RA), plays a role in learning and memory and has been shown to reduce amyloid-beta plaques and rescue learning deficits associated with AD. However, the rapid metabolism of RA by hydrolase CYP26 results in a short half-life. We propose CYP26 inhibition to cause an increase in endogenous RA. Increased concentrations of RA in the brain increase the retinoic acid receptor (RAR) and retinoic x receptor (RXR) signaling pathways which contribute to learning and memory. RAR/RXR signaling plays a critical role in learning, memory and long-term potentiation by mediating synaptic transmission and potentiation in the hippocampus. With the use of a mouse model, a novel CYP26 inhibitor can be tested using pharmacokinetic and behavioral studies, such as the Morris water maze and Y maze, as a basis to measure its effectiveness as a treatment method of AD.

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Apr 11th, 4:00 PM Apr 11th, 4:20 PM

Novel CYP26 Inhibitors as a Treatment for Alzheimer’s Disease

More than 5 million Americans are living with Alzheimer’s Disease (AD) and an American develops AD every 68 seconds. With no cures or significantly effective treatments available the number of Americans with AD is estimated to reach 7.1 million in 2025. AD is characterized by the increase in beta-amyloid plaques located in the extracellular space between the brain’s nerve cells. The endogenous chemical, retinoic acid (RA), plays a role in learning and memory and has been shown to reduce amyloid-beta plaques and rescue learning deficits associated with AD. However, the rapid metabolism of RA by hydrolase CYP26 results in a short half-life. We propose CYP26 inhibition to cause an increase in endogenous RA. Increased concentrations of RA in the brain increase the retinoic acid receptor (RAR) and retinoic x receptor (RXR) signaling pathways which contribute to learning and memory. RAR/RXR signaling plays a critical role in learning, memory and long-term potentiation by mediating synaptic transmission and potentiation in the hippocampus. With the use of a mouse model, a novel CYP26 inhibitor can be tested using pharmacokinetic and behavioral studies, such as the Morris water maze and Y maze, as a basis to measure its effectiveness as a treatment method of AD.