@article{10.37349/en.2025.100672,
abstract = {Intracellular amyloid β oligomers (AβOs) have been linked to Alzheimer's disease (AD) pathogenesis and to the neuronal damage in this neurodegenerative disease. Calmodulin, which binds AβO with very high affinity, plays a pivotal role in Aβ-induced neurotoxicity and has been used as a model template protein for the design of AβO-antagonist peptides. The hydrophobic amino acid residues of the COOH-terminus domain of Aβ play a leading role in its interaction with the intracellular proteins that bind AβO with high affinity. This review focuses on Aβ-antagonist hydrophobic peptides that bind to the COOH-terminus of Aβ and their endogenous production in the brain, highlighting the role of the proteasome as a major source of this type of peptides. It is emphasized that the level of these hydrophobic endogenous neuropeptides undergoes significant changes in the brain of AD patients relative to age-matched healthy individuals. It is concluded that these neuropeptides may become helpful biomarkers for the evaluation of the risk of the onset of sporadic AD and/or for the prognosis of AD. In addition, Aβ-antagonist hydrophobic peptides that bind to the COOH-terminus of Aβ seem a priori good candidates for the development of novel AD therapies, which could be used in combination with other drug-based therapies. Future perspectives and limitations for their use in the clinical management of AD are briefly discussed.},
author = {Gutierrez-Merino, Carlos},
doi = {10.37349/en.2025.100672},
journal = {Exploration of Neuroscience},
elocation-id = {100672},
title = {Anti-amyloid β hydrophobic peptides in Alzheimer's disease: biomarkers and therapeutic potential},
url = {https://www.explorationpub.com/Journals/en/Article/100672},
volume = {4},
year = {2025}
}