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Learning process to be regulated by altering brain protein

by Medindia Content Team on Aug 18 2005 12:44 PM

Identification of a new biochemical switch that affects how neurons fire in a part of the brain associated with learning could pave way for better understanding of schizophrenia and Alzheimer's disease.

A protein named “ Reelin”, an important component of the nervous system has been the focus of the research. During development, reelin sends cues to migrating neurons, telling them where they're supposed to go. In adult mice, reelin has recently been implicated in the formation of memories. Reduced production of the protein has been associated with schizophrenia in humans. Emphasis has been laid on a specific area of the brain called the hippocampus, which is important for learning. The interaction of reelin and two other molecules, Apoer2 and the NMDA receptor has also been studied. In the nervous system, the NMDA receptor is embedded in the gaps between nerve cells - where it is involved in receiving signals from other nerve cells. Apoer2 is another receptor, which is associated with the NMDA receptor. When reelin encounters the cell, it attaches to Apoer2, which then boosts the activity of the NMDA receptor by promoting a chemical modification of the part of the NMDA receptor inside the cell. The result of this modification is that signals being received by the nerve cell are amplified - and better reception means better learning. This transition in the primary function of Apoer2, from guiding neurons in the embryonic brain to regulating synaptic signaling, occurs around the time of birth. A small string of amino acids gets added near one end of Apoer2 and is essential for this new function. This longer form of Apoer2 is necessary for reelin to act upon the NMDA receptor. When reelin binds to the longer Apoer2, the NMDA receptor alters its structure and actions, resulting in the strengthening of the signals the nerve cells receive. In addition to reelin, Apoer2 binds to a protein called ApoE. One form of this molecule, called ApoE4, has been shown to substantially increase the risk of Alzheimer's disease in older people. Understanding how ApoE4 functions in the brain and interacts with ApoE receptors, such as Apoer2, is critical for gaining further insight into the mysterious mechanisms that causes neurodegenerative disease.


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