AI Platform Identifies Traditional Chinese Medicine Compounds for Alzheimer's Disease Treatment
核心洞察
University of Macau researchers developed an AI platform integrating a million-compound library to discover bioactive ingredients in traditional Chinese medicine for Alzheimer's disease treatment.
The platform efficiently identifies TCM compounds with neuroprotective activity, autophagy-modulating properties, and favorable blood-brain barrier permeability through virtual screening and cross-species validation.
Several candidate compounds have demonstrated promising effects in animal models and target mTOR (搜索)-independent autophagic pathways to promote clearance of toxic proteins.
A research team at the University of Macau has developed an artificial intelligence platform that could revolutionize traditional Chinese medicine drug discovery for Alzheimer's disease, potentially addressing a critical gap in treatment options for the more than 50 million people worldwide suffering from this devastating neurodegenerative condition.
The AI-driven platform, developed by a team led by Lu Jiahong, deputy director of the Institute of Chinese Medical Sciences at the University of Macau, in collaboration with Hangzhou MindRank AI Technology Co Ltd and Imperial College London, integrates a million-compound library with multiple predictive modules to identify bioactive ingredients in traditional Chinese medicine and natural products. The findings were published in Nature Biomedical Engineering.
Addressing Traditional Screening Limitations
Traditional Chinese medicine and natural products have long served as important sources of drug innovation, but their chemical complexity and vast number of constituents have made conventional screening methods time-consuming and labor-intensive, hindering TCM modernization. The new AI platform overcomes these bottlenecks by seamlessly integrating advanced algorithms and computational models.
The platform can efficiently identify TCM ingredients with three critical properties for Alzheimer's treatment: neuroprotective activity, autophagy-modulating properties, and favorable blood-brain barrier permeability. Through virtual screening followed by cross-species experimental validation, researchers have successfully identified small-molecule TCM compounds with therapeutic potential for Alzheimer's disease.
Platform Evolution and Performance
The platform represents the culmination of iterative development, with the first generation results published in Nature Biomedical Engineering in 2022. The current version has significantly expanded its natural product and TCM compound library to encompass millions of entries, while substantially improving both screening speed and accuracy.
Several candidate compounds identified through the platform have already demonstrated promising effects in animal models of Alzheimer's disease and are currently undergoing further development, indicating the platform's practical therapeutic potential.
Targeting Autophagy Dysfunction
The research addresses a fundamental challenge in Alzheimer's treatment. While drug development targeting traditional Alzheimer's targets has faced persistent difficulties, and recently approved amyloid-targeting antibody drugs offer only limited cognitive benefits with notable side effects, the field has lacked major therapeutic breakthroughs.
Autophagy, a highly conserved cellular "waste clearance" mechanism that degrades and recycles damaged proteins and old organelles, is essential for maintaining neuronal homeostasis. Numerous studies have demonstrated that autophagic dysfunction in Alzheimer's patients' brains leads to the accumulation of toxic substances, including β-amyloid and hyperphosphorylated tau, which exacerbate neurodegeneration.
The candidate TCM small molecules identified in this study can precisely modulate an mTOR (搜索)-independent autophagic pathway, promoting the clearance of toxic proteins and thereby slowing disease progression. This approach represents a highly promising new strategy for treating Alzheimer's disease by restoring or enhancing autophagy.
Public Availability and Future Impact
The AI platform is now publicly available at https://deepdrugdiscovery.mindrank.ai/, with the aim of facilitating TCM mechanism elucidation, accelerating innovative drug discovery, and providing technical support for TCM modernization and internationalization.
The research was supported by multiple funding sources, including the University of Macau-Dr. Stanley Ho Medical Development Foundation, the National Natural Science Foundation of China, the Science and Technology Development Fund of the Macao SAR, and the University of Macau Development Foundation.
The study's corresponding authors are Professor Lu and Niu Zhangming, CEO of Hangzhou MindRank AI Technology Co Ltd, with co-first authors including postdoctoral fellows Dong Yu and Zhuang Xuxu from the University of Macau, as well as Xiao Xianglu and Yu Wenfan from Hangzhou MindRank AI Technology Co Ltd.