Journal
ACS CHEMICAL NEUROSCIENCE
Volume 12, Issue 22, Pages 4249-4256Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.1c00600
Keywords
Amyloid; neuroinflammation; microglia; EphA4; ubiquitin proteasome system; angiogenesis
Funding
- Research Grants Council of Hong Kong [16102019, 16100418, 16149616]
- Area of Excellence Scheme of the University Grants Committee [AoE/M-604/16]
- Theme-based Research Scheme [T13-605/18W]
- Health and Medical Research Fund [HMRF15SC16]
- Innovation and Technology Commission [ITCPD/17-9, UIM/198, UIM/375]
- S. H. Ho Foundation
Ask authors/readers for more resources
The study found that rhynchophylline can improve amyloid plaque burden and reduce inflammation in an Alzheimer's disease mouse model. Transcriptome analysis revealed that rhynchophylline regulates multiple molecular pathways associated with amyloid metabolism and inflammation, suggesting potential therapeutic benefits for Alzheimer's disease.
Alzheimer's disease (AD), the most common neurodegenerative disease, has limited treatment options. As such, extensive studies have been conducted to identify novel therapeutic approaches. We previously reported that rhynchophylline (Rhy), a small molecule EphA4 inhibitor, rescues impaired hippocampal synaptic plasticity and cognitive dysfunctions in APP/PS1 mice, an AD transgenic mouse model. To assess whether Rhy can be developed as an alternative treatment for AD, it is important to examine its pharmacokinetics and effects on other disease-associated pathologies. Here, we show that Rhy ameliorates amyloid plaque burden and reduces inflammation in APP/PS1 mice. Transcriptome analysis revealed that Rhy regulates various molecular pathways in APP/PS1 mouse brains associated with amyloid metabolism and inflammation, specifically the ubiquitin proteasome system, angiogenesis, and microglial functional states. These results show that Rhy, which is blood-brain barrier permeable, is beneficial to amyloid pathology and regulates multiple molecular pathways.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available