Visit our Expo - Redox and Inflammation signaling 2012

Session XII : Cell death and neurodegenerative diseases Poster XII, 19
Amyloid precursor protein and Presenilin 1 interaction in human H4cells studied by
FLIM and FRET.
Mario Nizzari1, Valentina Venezia1, Paolo Bianchini2, Valentina Caorsi2, Alberto
Diaspro2, Emanuela Repetto1, Stefano Thellung1, Alessandro Corsaro1, Gennaro
Schettini1, Pia Carlo1, Tullio Florio1 and Claudio Russo3.
1Pharmacology, Dept. Oncology, Biology and Genetics, 2LAMBS-MicroscoBio, Dept
Physics, Univ Genova, Italy, 3Dept. of Health Sciences Univ Molise. e-mail:
mario.nizzari@unige.it
The pathologic hallmarks of Alzheimer’s disease (AD) are senile plaque and neurofibrillary
tangles. Senile plaque are primilary made up of deposits of amyloid-beta protein, a proteolytic
product derived from the amyloid precursor protein (APP). APP is a transmembrane protein
inserted into the endoplasmic reticulum, transported to the Golgi apparatus, to the cell surface,
and recycled by endocytosis to endosomes. Proteolytic processing, lead at the formation of
amyloid-beta protein, and a C-terminal fragments (CTFs). It’s not fully understood where
amyloid-beta is generated. However the identification of presenilins (PS), a component of
gamma secretase complex that cleave CTFs, leaving 40 or 42 amino acids amyloid-beta
peptides and 58 or 56 amino acids intracellular domains (AICD), provides a opportunity to
study APP-Presenilin interaction in specific cell compartments. In our study we used two
biophysical assays of protein proximity: fluorescence resonance energy transfer (FRET), and
fluorescence lifetime immaging microscopy (FLIM), that can provide information about
molecular interactions when two proteins are in the close proximity (of