Alzheimer's disease (AD), which is predicted to affect 1 in 85 persons worldwide by 2050, results in progressive loss of neuronal functions, leading to impairments in memory and cognitive abilities. As being one of the major neuropathological hallmarks of AD, senile plaques mainly consist of amyloid-β (Aβ) peptides, which are derived from amyloid precursor protein (APP) via the sequential cleavage by β- and γ-secretases. Although the overproduction and accumulation of Aβ peptides are at the center of AD research, the new discoveries point out to the complexity of the disease development. In this respect, it is crucial to understand the processing and the trafficking of APP, the enzymes involved in its processing, the cleavage products and their therapeutic potentials. This review summarizes the salient features of APP processing focusing on APP, the canonical secretases as well as the novel secretases and the cleavage products with an update of the recent developments. We also discussed the intracellular trafficking of APP and secretases in addition to their potential in AD therapy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejphar.2019.172415 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Plasma amyloid-β precursor protein /amyloid-β ratio is associated with cognition in Alzheimer's disease.
J Prev Alzheimers Dis
January 2025
Department of Neurology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan. Electronic address:
Plasma amyloid-β (Aβ) markers are significant predictors of Aβ pathology. However, their prognostic value for cognition in patients with Alzheimer's disease (AD) is unknown. We compared plasma amyloid-β precursor protein (APP) and Aβ levels between cognitively unimpaired participants (CU) and those with MCI due to AD and AD dementia.
View Article and Find Full Text PDFBioinformatics and Deep Learning Approach to Discover Food-Derived Active Ingredients for Alzheimer's Disease Therapy.
Foods
January 2025
Department of Bioconvergence, Hoseo University, Asan 31499, Republic of Korea.
Alzheimer's disease (AD) prevention is a critical challenge for aging societies, necessitating the exploration of food ingredients and whole foods as potential therapeutic agents. This study aimed to identify natural compounds (NCs) with therapeutic potential in AD using an innovative bioinformatics-integrated deep neural analysis approach, combining computational predictions with molecular docking and in vitro experiments for comprehensive evaluation. We employed the bioinformatics-integrated deep neural analysis of NCs for Disease Discovery (BioDeepNat) application in the data collected from chemical databases.
View Article and Find Full Text PDFEvaluation of the Anti-Amyloid and Anti-Inflammatory Properties of a Novel Vanadium(IV)-Curcumin Complex in Lipopolysaccharides-Stimulated Primary Rat Neuron-Microglia Mixed Cultures.
Int J Mol Sci
December 2024
Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Lipopolysaccharides (LPS) are bacterial mediators of neuroinflammation that have been detected in close association with pathological protein aggregations of Alzheimer's disease. LPS induce the release of cytokines by microglia and mediate the upregulation of inducible nitric oxide synthase (iNOS)-a mechanism also associated with amyloidosis. Curcumin is a recognized natural medicine but has extremely low bioavailability.
View Article and Find Full Text PDFFecal microbiota transplantation attenuates Alzheimer's disease symptoms in APP/PS1 transgenic mice via inhibition of the TLR4-MyD88-NF-κB signaling pathway-mediated inflammation.
Behav Brain Funct
January 2025
Wenzhou Key Laboratory of Sanitary Microbiology; School of Laboratory Medicine and Life Sciences; Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
Alzheimer's disease (AD) is a prevalent and progressive neurodegenerative disorder that is the leading cause of dementia. The underlying mechanisms of AD have not yet been completely explored. Neuroinflammation, an inflammatory response mediated by certain mediators, has been exhibited to play a crucial role in the pathogenesis of AD.
View Article and Find Full Text PDFChemerin-9 is neuroprotective in APP/PS1 transgenic mice by inhibiting NLRP3 inflammasome and promoting microglial clearance of Aβ.
J Neuroinflammation
January 2025
Department of Neurology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Yishan Road 600, Shanghai, 200233, China.
Background: Alzheimer's disease (AD) is a prevalent neurodegenerative disorder worldwide, and microglia are thought to play a central role in neuroinflammatory events occurring in AD. Chemerin, an adipokine, has been implicated in inflammatory diseases and central nervous system disorders, yet its precise function on microglial response in AD remains unknown.
Methods: The APP/PS1 mice were treated with different dosages of chemerin-9 (30 and 60 µg/kg), a bioactive nonapeptide derived from chemerin, every other day for 8 weeks consecutively.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!