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This theory is based on the fact that glutamate an amino acid present in proteins can cause neuronal cell death when present in high concentration The specific evidence for the excitotoxic theory comes from the demonstration of decreased levels of glutamate in ALS spinal cord with the assumption that glutamate must have been released and must have been present in high concentrations that would have been toxic In addition there is a decreased ability of glutamate to be taken up in fractions of spinal cord tissue of ALS patients taken at autopsy Such data would suggest once again that glutamate might have been elevated as a result of a failure of uptake However the changes in glutamate could also be secondary to damage or loss of motor neurons Thus it is not clear what triggers the release of glutamate and the failure of glutamate uptake Nevertheless the fact that glutamate can be toxic for motor neurons does suggest that glutamate may play a role if not in causing ALS then possibly as a participant in motor neuron injury Recent research has documented that the growth and maintenance of motor neurons are dependent on protein nutritive hormones called neurotrophic factors Insulin like growth factor-1 IGF-1 ciliary neurotrophic factor CNTF and brain-derived neurotrophic factor BDNF are all examples of such neurotrophic factors which have been documented to influence motor neuron development and maintenance In addition such factors appear to influence the regenerative and repair capacity of motor neurons IGF-1 is now considered to be the major factor which produces sprouting of nerves in man These neurotrophic factors have considerable potential in motor neuron repair and could possibly function as neuroprotective agents and play a meaningful role in therapyiopsy of affected tissue early in disease is often a
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