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Alzheimer’s Disease Acetylcholine Presentation by: Huy Nguyen Chemistry 12B Instructor: Dr. Adamczeski Fall-2006 Out line What is Acetylcholine? Synthesis of Acetylcholine How does Acetylcholine work in nervous system Acetylcholine receptors Degradation of Acetylcholine Alzheimer’s disease Drug development Reference What is Acetylcholine? The first known neurotransmitter, discovered in 1920’s. It is the neurotransmitter at nerve-muscle connections and at nervous system synapses. An organic compound: CH3CO2CH2CH2N+(CH3)3 Synthesis of Acetylcholine (Ach) Acetylcholine is a simple molecule synthesized from choline and acetyl-CoA through the action of choline acetyltransferase in cholinergic neurons. Acetyl-CoA Choline How does Ach work in nervous system? Action potential reaches the terminal button of a presynaptic neuron. Ca2+, stimulates the exocytosis of vesicles containing Ach, which is released into the synaptic cleft. Ach reaches the other neuron membrane, then binds to the Ach receptors and activates them to open ion channels to create new action potential. Acetylcholine receptors Nicotinic receptors: S – Nicotine: C10H14N2 Acetylcholine receptors Muscarinic receptors Muscarine: C9H20ON + Alzheimer’s Disease The cause of Alzheimers Disease is not fully understood. It is believed there may be genetic (hereditary) factors involved, with a breakdown of proteins resulting in the formation of protein deposits (senile plaques) within the brain. Acetylcholine is required for the normal functioning of the brain cells and, as levels of the chemical decrease, plaques form creating bundles of fibers (neurofibrillary tangles). Alzheimer’s disease is characterized by amyloid plaques (clumps of fibers) and tangles of fibers in brain. Alzheimer’s disease may disrupt normal thinking and memory by blocking the massages transferred through neurons by neurotransmitter