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2013 Grants - Kessels
Amyloid Beta Targets Synapses Based on AMPA Receptor Subunit Composition
Helmut Kessels, Ph.D.
Netherlands Institute for Neuroscience-KNAW
2013 New Investigator Research Grant
Beta-amyloid (also known as amyloid beta) is a protein fragment that is toxic to nerve cells. One of the effects of beta-amyloid on nerve cells is impairment of synapses, specialized parts of nerve cells that communicate with other nerve cells and give the nervous system many of its unique capabilities, including learning and memory.
When a nerve cell sends a signal to another nerve cell, it releases a small packet of a hormone-like chemical (neurotransmitter) into the synapse. That chemical binds to proteins on the receiving cell causing that cell to become active or suppressed. The proteins receiving the signal are known as receptors. Some of the most common types of receptors in the brain are known as AMPA receptors because they can be identified by their response to an artificial chemical called AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid). Several types of AMPA receptors have been identified.
Helmut Kessels, Ph.D., and colleagues have found preliminary evidence that cells with certain types of AMPA receptors are more susceptible to beta-amyloid toxicity than cells with other types of AMPA receptors. This susceptibility may cause greater beta-amyloid toxicity in certain cells compared to other cells. Furthermore, they have evidence that synapses in less-susceptible cells have had less exposure to signals inducing learning and memory. The researchers plan to conduct additional experiments to test and confirm these observations. These studies may help to identify potential drug targets to prevent or slow the progression of synaptic damage in Alzheimer's disease.