Insights & Perspectives
A new molecular explanation for age-related neurodegeneration: The Tyr682 residue of amyloid precursor protein
Article first published online: 14 AUG 2013
© 2013 The Author. Bioessays published by WILEY Periodicals, Inc.
This is an open access article under the terms of the Creative Commons Attribution Non–Commercial–NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non–commercial and no modifications or adaptations are made.
Volume 35, Issue 10, pages 847–852, October 2013
How to Cite
Matrone, C. (2013), A new molecular explanation for age-related neurodegeneration: The Tyr682 residue of amyloid precursor protein. Bioessays, 35: 847–852. doi: 10.1002/bies.201300041
- Issue published online: 14 SEP 2013
- Article first published online: 14 AUG 2013
- Lunbeck Foundation. Grant Number: R108-A10719
- abeta peptides;
- adaptor proteins;
- YENPTY domain
Emerging evidence supports the role for the intracellular domains of amyloid precursor protein (APP) in the physiology and function of APP. In this short report, I discuss the hypothesis that mutation of Tyr682 on the Y682ENPTY687 C-terminal motif of APP may be directly or indirectly associated with alterations in APP functioning and activity, leading to neuronal defects and deficits. Mutation of Tyr682 induces an early and progressive age-dependent cognitive and locomotor decline that is associated with a loss of synaptic connections, a decrease in cholinergic tone, and defects in NGF signaling. These findings support a model in which APP-C-terminal domain exerts a pathogenic function in neuronal development and decline, and suggest that Tyr682 potentially could modulate the properties of APP metabolites in humans.