Evaluation and targeting of amyloid precursor protein (APP)/amyloid beta (Aβ) axis in amyloidogenic and non-amyloidogenic pathways: A time outside the tunnel.

In Alzheimer disease (AD), amyloid precursor protein (APP) and production of amyloid beta (Aβ) which is generated by amyloidogenic pathway is implicated in neurotoxicity and neuronal cell deaths. However, physiological Aβ level is essential to improves neuronal survival, attenuates neuronal apoptosis and has neuroprotective effect. In addition, physiological APP level has neurotrophic effect on the central nervous system (CNS). APP has a critical role in the brain growth and development via activation of long-term potentiation (LTP) and acceleration of neurite outgrowth. Moreover, APP is cleaved by α secretase to form a neuroprotective soluble APP alpha (sAPPα) in non-amyloidogenic pathway. Consequently, this mini-review purposes to highlight the possible beneficial role of APP and Aβ. In addition, this mini-review discussed the modulation of APP processing and Aβ production. • APP is a major source of Aβ peptide in the pathogenesis of AD. • APP is cleaved by ; amyloidogenic pathway which form Aβ, and non-amyloidogenic pathway which form the neuroprotective sAPPα. • Activation or inhibition of non-amyloidogenic pathways could be effective therapeutic strategy for AD. [ABSTRACT FROM AUTHOR]