The role of APP in Alzheimer’s disease

Abstract

Alzheimer's disease (AD) is one of the most significant neurodegenerative disorders in terms of both severity and cost. Despite being defined over a century ago, there is currently no cure to this disease that affects an increasing elderly population. The amyloid precursor protein (APP) has been shown to play an important role in AD progression. The amyloid β peptide (Aβ), which accumulates in senile plaques, a central etiological AD factor, is a proteolytic product from APP by the enzymatic action of βand γ-secretases. In this review, we summarize the current knowledge of the processing and physiological functions of APP, and the involvement of APP and Aβ in AD. . (1999) Mutagenesis identifies new signals for β-amyloid precursor protein endocytosis, turnover, and the generation of secreted fragments, including Aβ42.

Role of Nuclear Factor Kappa B (NF-κB) Signalling in Neurodegenerative Diseases: An Mechanistic Approach

“…Normally, the enzyme alpha-secretase cleaves the extracellular domain and gamma-secretase cleaves the APP into discrete fragments which are soluble [ 137 ]. In Alzheimer pathological condition, the enzyme called beta-secretase (BACE) or beta–site amyloid precursor protein cleaving enzyme 1 (BACE1) initiates the production of the amyloid beta with another protease called gamma-secretase that cleaves the upper part extracellular domain of the APP which is the N- terminus of the amyloid-beta and the gamma–secretase cleaves the C terminal of beta-amyloid [ 138 ]. The left-over fragment is insoluble and creates the monomers called Amyloid beta, which is no longer regulated.…”

FoxO mediates APP-induced AICD-dependent cell death

“…Alzheimer's disease (AD), characterized by a progressive cognitive decline leading to social and occupational debilitation, has been regarded as the most prevalent neurodegenerative disease in the world. 1 AD is pathologically differentiated from other causes of dementia by a reduction in synaptic contact, 2 accumulation of neurofibrillary tangles, 3 , 4 aggregates of the hyper-phosphorylated microtubule-associated protein tau, 5 and extracellular senile plaques (SPs) containing the amyloid β peptide (A β ). 6 Although senior individuals often develop some plaques and tangles as a consequence of aging, the brains of AD patients have a greater number of them in specific brain regions such as the temporal lobe.…”