Functions of APP and APP derived-fragments

Yuhki Saito, Toshiharu Suzuki

Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University

The β-amyloid protein precursor (APP) is a key molecule involved in the pathogenesis of Alzheimer's disease. APP is primary cleaved by α- and β-secretase to generate C-terminal fragments (CTFα and CTFβ) and secretes large N-terminal fragments (sAPPα and sAPPβ). The membrane-bound CTFs are further subjected to second cleavage by γ-secretase complex. There are growing evidences that APP and its fragments have various roles in synapse formation and functions. To understand the physiological functions of APP and its fragments are important for developing the medicine against Alzheimer's disease with less side effects. This review summarizes the recent insights of physiological roles of APP, APLPs, and APP-derived fragments (sAPP, CTF, Aβ, and AICD).

Address correspondence to Dr. Yuhki Saito, Laboratory of Neuroscience, Graduate School of Pharmaceutical Sciences, Hokkaido University (Kita 12, Nishi 6, Kita-Ku, Sapporo 060-0812, Japan)