Excitotoxicidad

Excitotoxicidad refers to the pathological process by which nerve cells are damaged or killed as a result of excessive stimulation by excitatory neurotransmitters, particularly glutamate. Glutamate is the primary excitatory neurotransmitter in the central nervous system, playing crucial roles in learning, memory, and synaptic plasticity. However, under pathological conditions, such as stroke, traumatic brain injury, or neurodegenerative diseases, excessive glutamate release or impaired glutamate reuptake can lead to its accumulation in the synaptic cleft.

This sustained high concentration of glutamate overstimulates glutamate receptors, particularly the N-methyl-D-aspartate (NMDA) receptors and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Activation of these receptors leads to an excessive influx of calcium ions (Ca2+) into the postsynaptic neuron. The overwhelming increase in intracellular calcium triggers a cascade of harmful events, including the activation of enzymes that degrade cellular components, the generation of reactive oxygen species, and ultimately, programmed cell death (apoptosis) or necrosis.

The concept of excitotoxicity was first proposed in the 1960s and has since become a significant area of research in neuroscience. It is implicated in a wide range of neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), epilepsy, and stroke. Understanding the mechanisms of excitotoxicity is crucial for developing therapeutic strategies aimed at protecting neurons from glutamate-induced damage and potentially slowing or preventing the progression of these debilitating conditions. Research efforts focus on developing drugs that can block glutamate receptors, enhance glutamate uptake, or interfere with the downstream signaling pathways activated by excessive calcium influx.