THERAPEUTIC TARGETING OF AMYLOID PRECURSOR PROTEIN TYROSINE 682 RESIDUE IN ALZHEIMER’S DISEASE

2020.12.03 | Graduate School of Health

Thursday 17 December at 14:00, Filomena Iannuzzi defends her PhD dissertation entitled "THERAPEUTIC TARGETING OF AMYLOID PRECURSOR PROTEIN TYROSINE 682 RESIDUE IN ALZHEIMER’S DISEASE".

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder that currently has no cure and no effective treatment. The amyloid precursor protein (APP) is one of most extensively studied molecules in AD, as its cleavage leads to dysregulated production of Aβ peptides, which together with tau protein are considered the two central players in AD. APP cleavage depends on its intracellular location. Phosphorylation of the APP Tyr682 residue, located on the 682YENPTY687 C-terminal motif, regulates APP compartmentalisation and controls APP cleavage. This PhD project proposes the excessive phosphorylation of the APP Tyr682 residue as responsible for Aβ42 production and accumulation and points on Fyn tyrosine kinase (TK) as crucial in mediating APP Tyr682 phosphorylation in neurons from AD patients. Indeed, hyperactivated Fyn and elevated APP Tyr682 phosphorylation levels are found in neurons, fibroblasts and blood samples from AD patients. Fyn TK inhibitors decrease APP Tyr682 phosphorylation and reduced Aβ42 release in media from neurons of AD patients.Taken together, the results of this PhD project suggest the APP Tyr682 residue as molecular target for either the development of diagnostic procedures in patients at early stages of the AD or to the design of a pharmacologic personalized therapy using Fyn TK inhibitors.

The summary is written by the PhD student.    

The defence is public and will be online via Zoom (https://aarhusuniversity.zoom.us/j/63928654976). Please read the attached press release for more information.

Contact:

PhD student Filomena Iannuzzi

Mail: filomena.iannuzzi@biomed.au.dk

Phone: (+39) 3318289619

Read full press release