1.Artificial intelligence in drug development for delirium and Alzheimer's disease.
Ruixue AI ; Xianglu XIAO ; Shenglong DENG ; Nan YANG ; Xiaodan XING ; Leiv Otto WATNE ; Geir SELBÆK ; Yehani WEDATILAKE ; Chenglong XIE ; David C RUBINSZTEIN ; Jennifer E PALMER ; Bjørn Erik NEERLAND ; Hongming CHEN ; Zhangming NIU ; Guang YANG ; Evandro Fei FANG
Acta Pharmaceutica Sinica B 2025;15(9):4386-4410
Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer's disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.
2.Autophagy, Cellular Aging and Age-related Human Diseases
So Yeong CHEON ; Hyunjeong KIM ; David C RUBINSZTEIN ; Jong Eun LEE
Experimental Neurobiology 2019;28(6):643-657
Macroautophagy/autophagy is a conserved degradation system that engulfs intracytoplasmic contents, including aggregated proteins and organelles, which is crucial for cellular homeostasis. During aging, cellular factors suggested as the cause of aging have been reported to be associated with progressively compromised autophagy. Dysfunctional autophagy may contribute to age-related diseases, such as neurodegenerative disease, cancer, and metabolic syndrome, in the elderly. Therefore, restoration of impaired autophagy to normal may help to prevent age-related disease and extend lifespan and longevity. Therefore, this review aims to provide an overview of the mechanisms of autophagy underlying cellular aging and the consequent disease. Understanding the mechanisms of autophagy may provide potential information to aid therapeutic interventions in age-related diseases.
Aged
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Aging
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Autophagy
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Cell Aging
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DNA Damage
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Homeostasis
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Humans
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Longevity
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Neurodegenerative Diseases
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Organelles
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Oxidative Stress
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Telomere Shortening

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