Related Experiment Video
Updated: Aug 11, 2025
Assessment of Spontaneous Alternation, Novel Object Recognition and Limb Clasping in Transgenic Mouse Models of Amyloid-β and Tau Neuropathology
Published on: May 28, 2017
Uncovering the Oxidative Stress Mechanisms and Targets in Alzheimer's Disease by Integrating Phenotypic Screening
Moran Zhou1, Qian Jiao1, Zengrui Wu1
1Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
Background:
The oxidative stress hypothesis is challenging the dominant position of amyloid-β (Aβ) in the field of understanding the mechanisms of Alzheimer's disease (AD), a complicated and untreatable neurodegenerative disease.
Objective:
The goal of the present study was to uncover the oxidative stress mechanisms causing AD, as well as the potential therapeutic targets and neuroprotective drugs against oxidative stress mechanisms.
Methods:
In this study, a systematic workflow combining pharmacological experiments and computational prediction was proposed. 222 drugs and natural products were collected first and then tested on SH-SY5Y cells to obtain phenotypic screening data on neuroprotection. The preliminary screening data were integrated with drug-target interactions (DTIs) and multi-scale biomedical data, which were analyzed with statistical tests and gene set enrichment analysis. A polypharmacology network was further constructed for investigation.
Results:
340 DTIs were matched in multiple databases, and 222 cell viability ratios were calculated for experimental compounds. We identified significant potential therapeutic targets based on oxidative stress mechanisms for AD, including NR3C1, SHBG, ESR1, PGR, and AVPR1A, which might be closely related to neuroprotective effects and pathogenesis. 50% of the top 14 enriched pathways were found to correlate with AD, such as arachidonic acid metabolism and neuroactive ligand-receptor interaction. Several approved drugs in this research were also found to exert neuroprotective effects against oxidative stress mechanisms, including beclometasone, methylprednisolone, and conivaptan.
Conclusion:
Our results indicated that NR3C1, SHBG, ESR1, PGR, and AVPR1A were promising therapeutic targets and several drugs may be repurposed from the perspective of oxidative stress and AD.
Insights
This study explores oxidative stress in Alzheimer's disease (AD), identifying new therapeutic targets like NR3C1 and potential drug repurposing for neuroprotection against AD.
Area of Science:
- Neuroscience
- Pharmacology
- Computational Biology
Background:
- Alzheimer's disease (AD) is a complex neurodegenerative disorder.
- The amyloid-beta (Aβ) hypothesis is being challenged by the oxidative stress hypothesis in AD research.
- Understanding oxidative stress mechanisms is crucial for developing new AD treatments.
Purpose of the Study:
- To investigate oxidative stress mechanisms underlying Alzheimer's disease.
- To identify potential therapeutic targets for AD.
- To discover neuroprotective drugs for oxidative stress-related mechanisms in AD.
Main Methods:
- A systematic workflow combining pharmacological experiments and computational prediction was employed.
- 222 drugs and natural products were screened for neuroprotective effects on SH-SY5Y cells.
- Drug-target interactions (DTIs) and multi-scale biomedical data were integrated and analyzed, including polypharmacology network construction.
Main Results:
- 340 DTIs were identified, and cell viability ratios for 222 compounds were calculated.
- Potential therapeutic targets for AD related to oxidative stress, including NR3C1, SHBG, ESR1, PGR, and AVPR1A, were identified.
- Enriched pathways correlated with AD, and several approved drugs (beclometasone, methylprednisolone, conivaptan) showed neuroprotective effects.
Conclusions:
- NR3C1, SHBG, ESR1, PGR, and AVPR1A are promising therapeutic targets for AD.
- Drug repurposing for oxidative stress and AD is a viable therapeutic strategy.
- The study provides insights into oxidative stress mechanisms and potential treatments for Alzheimer's disease.
More Related Videos
06:41Quantitative Analysis of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Stabilization in a Neural Model of Alzheimer's Disease (AD)
Published on: January 10, 2025
09:47Author Spotlight: Advancing Alzheimer's Research – Exploring Early Detection and Multi-Omics Approaches
Published on: December 15, 2023
Related Concept Videos
01:26Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
01:22Alzheimer's Disease: Treatment
01:26Aging
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...