Excitotoxicity and neurological disorders: involvement of membrane phospholipids

Excitatory amino acids and their receptors play an important role in membrane phospholipid metabolism. Persistent stimulation of excitatory amino acid receptors by glutamate may be involved in neurodegenerative diseases and brain and spinal cord trauma. The molecular mechanism of neurodegeneration induced by excitatory amino acids is, however, not known. Excitotoxin-induced calcium entry causes the stimulation of phospholipases and lipases. These enzymes act on neural membrane phospholipids and their stimulation results in accumulation of free fatty acids, diacylglycerols, eicosanoids, and lipid peroxides in neurodegenerative diseases and brain and spinal cord trauma. Other enzymes, such as protein kinase C and calcium-dependent proteases, may also contribute to the neuronal injury. Excitotoxin-induced alterations in membrane phospholipid metabolism in neurodegenerative diseases and neural trauma can be studied in animal and cell culture models. These models can be used to study the molecular mechanisms of the neurodegenerative processes and to screen the efficacy of therapeutic drugs.