PRIN 2017 - 2017T9JNLT_004 - Resp. dr. Gian Carlo Bellenchi TARGETING TYR682 RESIDUE ON THE AMYLOID PRECURSOR PROTEIN FOR THE DEVELOPMENT OF DIAGNOSTIC AND THERAPEUTIC STRATEGIES IN ALZHEIMER'S DISEASE. (DSB.AD004.245)
Project areaNeuroscienze (DSB.AD004)
Structure responsible for the research project
Alzheimer's disease (AD) is the main cause of dementia among people 65 years of age and older, affecting more than 25 million
people worldwide with the number of people affected doubling every five years. AD presents a major health problem and a
heavy economic burden in industrialized countries.
This project is designed to provide new target(s) for the development of novel diagnostic and therapeutic strategies for AD.
We hypothesize that the aberrant and cumulative amyloid beta (Abeta) production, considered one of the main etiological
causes of AD, is due to alterations in APP trafficking in neurons.
We reported that the Tyr682 residue -located on the APP 682-YENPTY-687 C-terminal domain- plays a crucial role in the
alterations of APP trafficking, thus controlling APP endocytosis and processing in neurons from mice and pigs.
We show that the APP Tyr682 is hyperphosphorylated in neuronal stem cells and fibroblasts from AD patients and that Fyn Tyr
kinase is responsible for such increased APP Tyr682 hyperphosphorylation (unpublished data).
Additionally, as previously reported in mice and pigs, the increased phosphorylation of APP Tyr682 residue causes altered APP
Start date of activity
Neuroscience, Neuropharmacology, Molecular medicine
Last update: 01/12/2023