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T14-encoding mRNA refers to the specific transcript of the acetylcholinesterase (AChE) gene, specifically the T-isoform (AChE-T), which contains the sequence for the bioactive 14-amino acid peptide T14. This peptide is proteolytically cleaved from the C-terminus of the AChE-T protein and functions as a signaling molecule that binds to an allosteric site on the alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR). In the developing brain, T14-mediated calcium signaling supports neuronal growth and plasticity; however, its aberrant reactivation in adulthood is a primary driver of neurodegeneration in conditions like Alzheimer's disease. The resulting chronic calcium influx leads to excitotoxicity, activation of the mTORC1 pathway, and the subsequent accumulation of amyloid-beta and phosphorylated tau. Therapeutic interventions, such as the cyclized peptide NBP14, aim to block the T14-receptor interaction to halt the neurodegenerative cascade.
NBP14 is a cyclized peptide antagonist that competitively binds to an allosteric site on the alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR), thereby displacing the T14 peptide and preventing calcium-induced excitotoxicity.
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