Final answer:
Normal huntingtin protein is involved in regulating glutamate receptor activity, preventing excitotoxicity caused by overstimulation of calcium-permeable AMPA receptors, which is linked to the pathogenesis and symptoms of Huntington's disease.
Step-by-step explanation:
The normal huntingtin protein helps to regulate the activity of glutamate receptors, which are crucial for synaptic transmission in the brain. Mutations in the huntingtin protein, which occur in Huntington's disease, lead to dysregulation of these receptors with potential excitotoxic effects. Calcium-permeable AMPA receptors, which are influenced by levels of glutamate and the RNA editing enzyme ADAR2, are associated with excitotoxicity when overstimulated. Studies indicate that in Huntington's disease, excessive activity of these receptors, especially at extrasynaptic sites, leads to increased intracellular calcium and cell death, in contrast to the beneficial effects of regulated, synaptic receptor activity. Thus, well-functioning huntingtin protein indirectly contributes to the downregulation or proper regulation of glutamate receptor activity, potentially preventing excitotoxicity.