AI Article Synopsis
- Alzheimer's disease (AD) is a leading neurodegenerative disorder often associated with aging, where increased production of amyloid-beta (Aβ) is crucial to its development.
- BACE1, the enzyme responsible for triggering Aβ formation, is influenced by neuronal activity, though the specific mechanisms involved were not fully understood until now.
- This research identifies Casein Kinase 2 as a key player in regulating BACE1 expression through the phosphorylation of eIF4B in neurons, suggesting a link between brain activity and Aβ production, which could lead to new treatment strategies for AD.
Article Abstract
Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. Increased Aβ production plays a fundamental role in the pathogenesis of the disease and BACE1, the protease that triggers the amyloidogenic processing of APP, is a key protein and a pharmacological target in AD. Changes in neuronal activity have been linked to BACE1 expression and Aβ generation, but the underlying mechanisms are still unclear. We provide clear evidence for the role of Casein Kinase 2 in the control of activity-driven BACE1 expression in cultured primary neurons, organotypic brain slices, and murine AD models. More specifically, we demonstrate that neuronal activity promotes Casein Kinase 2 dependent phosphorylation of the translation initiation factor eIF4B and this, in turn, controls BACE1 expression and APP processing. Finally, we show that eIF4B expression and phosphorylation are increased in the brain of APPPS1 and APP-KI mice, as well as in AD patients. Overall, we provide a definition of a mechanism linking brain activity with amyloid production and deposition, opening new perspectives from the therapeutic standpoint.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339060 | PMC |
| http://dx.doi.org/10.1038/s41419-021-04062-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Modulation of β secretase and neuroinflammation by biomimetic nanodelivery system for Alzheimer's disease therapy.
J Control Release
December 2024
Key Laboratory of Environmental Medicine Engineering of Ministry of Education, State Key Laboratory of Bioelectronics, Jiangsu Engineering Laboratory of Smart Carbon-Rich Materials and Device, School of Public Health, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 210009, PR China. Electronic address:
Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disorder. The vicious circle between amyloid-β peptide (Aβ) overgeneration and microglial dysfunction is an important pathological event that promotes AD progression. However, therapeutic strategies toward only Aβ or microglial modulation still have many problems.
View Article and Find Full Text PDFPharmacological inhibition of receptor protein tyrosine phosphatase β/ζ decreases Aβ plaques and neuroinflammation in the hippocampus of APP/PS1 mice.
Front Pharmacol
December 2024
Department of Health and Pharmaceutical Sciences, Faculty of Pharmacy, Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Madrid, Spain.
Alzheimer's disease (AD) is a major neurodegenerative disorder that courses with chronic neuroinflammation. Pleiotrophin (PTN) is an endogenous inhibitor of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ which is upregulated in different neuroinflammatory disorders of diverse origin, including AD. To investigate the role of RPTPβ/ζ in neuroinflammation and neurodegeneration, we used eight-to ten-month-old APP/PS1 AD mouse model.
View Article and Find Full Text PDFInhibitory Effects of Gliadin Hydrolysates on BACE1 Expression and APP Processing to Prevent Aβ Aggregation.
Int J Mol Sci
December 2024
Department of Nutrition, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung City 40604, Taiwan.
Alzheimer's disease (AD), a leading neurodegenerative disorder, is closely associated with the accumulation of amyloid-beta (Aβ) peptides in the brain. The enzyme β-secretase (BACE1), pivotal in Aβ production, represents a promising therapeutic target for AD. While bioactive peptides derived from food protein hydrolysates have neuroprotective properties, their inhibitory effects on BACE1 remain largely unexplored.
View Article and Find Full Text PDFNetwork Pharmacology, Molecular Docking, and In Vitro Insights into the Potential of for Alzheimer's Disease.
Int J Mol Sci
December 2024
School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand.
Korth. Havil (MS) has a traditional use in relieving pain, managing hypertension, treating cough, and diarrhea, and as a morphine substitute in addiction recovery. Its potential in addressing Alzheimer's disease (AD), a neurodegenerative condition with no effective treatments, is under investigation.
View Article and Find Full Text PDFBiochemical changes precede affective and cognitive anomalies in aging adult C57BL/6J mice with a prior history of adolescent alcohol binge-drinking.
Addict Biol
December 2024
Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, California, USA.
The early initiation of binge-drinking and biological sex are critical risk factors for the development of affective disturbances and cognitive decline, as well as neurodegenerative diseases including Alzheimer's disease. Further, a history of excessive alcohol consumption alters normal age-related changes in the pattern of protein expression in the brain, which may relate to an acceleration of cognitive decline. Here, we aimed to disentangle the interrelation between a history of binge-drinking during adolescence, biological sex and normal aging on the manifestation of negative affect, cognitive decline and associated biochemical pathology.
View Article and Find Full Text PDFWant 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!