Glutamate receptor
From Wikipedia,
http://en.wikipedia.org/wiki/Glutamate_receptorGlutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate is one of the 20 amino acids used to assemble proteins, so it is abundant in many areas of the body, but it also functions as a neurotransmitter and is particularly abundant in the nervous system. Glutamate receptors are responsible for the glutamate-mediated postsynaptic excitation of neural cells, and are important for neural communication, memory formation, learning, and regulation. Furthermore, glutamate receptors are implicated in the pathologies of a number of neurodegenerative diseases due to their central role in excitotoxicity and their prevalence throughout the central nervous system.
Excitotoxicity
Overstimulation of glutamate receptors causes neurodegeneration and neuronal damage through a process called excitotoxicity. Excessive glutamate, or excitotoxins acting on the same glutamate receptors, overactivate glutamate receptors (specifically NMDARs), causing high levels of calcium ions (Ca2+) to influx into the postsynaptic cell.[32]
Neurodegeneration
In the case of traumatic brain injury or cerebral ischemia (e.g. cerebral infarction or hemorrhage), acute neurodegeneration caused by excitotoxicity may spread to proximal neurons through two processes. Hypoxia and hypoglycemia trigger bioenergetic failure; mitochondria stop producing ATP energy. Na+/K+-ATPase can no longer maintain sodium/potassium ion concentration gradients across the plasma membrane. Glutamate transporters (EAATs), which use the Na+/K+ gradient, reverse glutamate transport (efflux) in affected neurons and astrocytes, and depolarization increases downstream synaptic release of glutamate.[38] In addition, cell death via lysis or apoptosis releases cytoplasmic glutamate outside of the ruptured cell.[39] These two forms of glutamate release cause a continual domino effect of excitotoxic cell death and further increased extracellular glutamate concentrations.
Neurodegenerative diseases
Glutamate receptors’ significance in excitotoxicity links it to many neurogenerative diseases. Conditions such as exposure to excitotoxins, old age, congenital predisposition, and brain trauma can trigger glutamate receptor activation and ensuing excitotoxic neurodegeneration. This damage to the central nervous system propagates symptoms associated with a number of diseases.[40]
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This article has much more detail and references to the Mouse Model in MS, but or and it refers allot to using Drugs to change the processes that involve Glutamate, rather than sorting out the original problem first!
Regards
Nigel