Abstract
The abnormal accumulation of amyloid-β (Aβ) in the central nervous system is a hallmark of Alzheimer’s disease (AD). The regulation of the processing of the single- transmembrane amyloid precursor protein (APP) plays an important role in the generation of Aβ in the brain. The phosphorylation of APP and key enzymes involved in the proteolytic processing of APP has been demonstrated to be critical for modulating the generation of Aβ by either altering the subcellular localization of APP or changing the enzymatic activities of the secretases responsible for APP processing. In addition, the phosphorylation may also have an impact on the physiological function of these proteins. In this review, we summarize the kinases and signaling pathways that may participate in regulating the phosphorylation of APP and secretases and how this further affects the function and processing of APP and Aβ pathology. We also discuss the potential of approaches that modulate these phosphorylation-signaling pathways or kinases as interventions for AD pathology.
Highlights
Current epidemiological studies estimate that there are approximately 45 million people suffering from dementia [1]
In Alzheimer’s disease (AD), the phosphorylation of amyloid precursor protein (APP) has been established at multiple levels, including both human and animal studies
The close link between the abnormal phosphorylation of proteins and AD pathology emphasizes that phosphorylation signaling pathways might be dysregulated during disease progression
Summary
Current epidemiological studies estimate that there are approximately 45 million people suffering from dementia [1]. Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a progressive decline in cognition and memory abilities in the elderly It has been identified as the leading cause of dementia, accounting for more than 60% of all dementia cases worldwide [3]. SNPs in genes regulating lipid homeostasis and immune function (e.g., phosphatidylinositol binding clathrin assembly protein (PICALM) for lipid metabolism and complement receptor type 1 (CR1) and triggering receptor expressed on myeloid cells 2 (TREM2) for immune regulation) have been associated with the risk of developing AD [1,10]. There are only four symptomatic treatments available for the management of AD-induced dementia Three of these drugs are cholinesterase inhibitors (ChEIs), which suppress the activity of cholinesterases in synaptic clefts and increase the content of acetylcholine in the brain, thereby improving memory and cognition [11]. The present review discusses the kinases and phosphorylation signaling during the metabolism of APP
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call