Acetylcholinesterase-derived C-terminal peptide (T14) (T14)

The T14 peptide is a 14-amino acid sequence (AEFHRWSSYMVHWK) derived from the C-terminus of the enzyme acetylcholinesterase (AChE) (Greenfield, 2013). It functions as a bioactive signaling molecule that binds to an allosteric site on the alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR), distinct from the enzyme's catalytic site (Garcia-Ratés et al., 2016). While it plays a neurotrophic role during brain development, its chronic elevation in the adult brain is associated with neurodegeneration, particularly in Alzheimer's disease (Greenfield et al., 2022). Pathological levels of T14 trigger excessive calcium influx through the alpha7-nAChR, leading to mitochondrial stress and neuronal apoptosis (Bonard et al., 2024). Therapeutic interventions, such as the cyclic peptide NBP14 and specific monoclonal antibodies, aim to neutralize T14 or block its receptor interaction to prevent neurotoxic signaling (NeuroBio, 2023). This peptide is considered a key driver of the isodendritic core neurodegeneration theory, which suggests a common mechanism for various dementias. Monitoring T14 levels in biofluids is also being explored as a diagnostic biomarker for early-stage neurodegenerative disease.

Other names

T14AChE-derived C-terminal peptideC-terminal acetylcholinesterase peptideT14 peptideAcetylcholinesterase C-terminal fragment

Neutralization of the T14 peptide or competitive inhibition of its binding to the alpha-7 nicotinic acetylcholine receptor to prevent pathological calcium influx.