澳大新語 • 2022 UMAGAZINE 25 55 學術研究 • ACADEMIC RESEARCH 隨著相關數據不斷積累，利用人工智能技術作虛擬藥 物篩選，有望代替傳統的活性篩選方法，不僅能加快 中間步驟，還可大幅降低研發成本，並且令藥物篩選 更精確。我們的團隊與合作方致力於前期應用人工智 能高效而低成本地篩選藥物，後期進行傳統的濕實驗 室驗證（細胞、線蟲和小鼠）提高篩藥準確性，兩者 結合可以加快藥物研發。這種設計思路不僅可用於AD 藥物開發，還可在不同的醫學領域應用。 善用人工智能開發藥物 現代藥物研發耗資巨大，從最初的生物活性篩選，到 發現先導化合物，再由科學家按經驗設計藥物及合成 化合物、分子生物學家測試化合物活性，經反覆優化 和篩選，最終發現臨床候選化合物，整個過程往往需 要10到20年。然而，這些化合物最終只有12%能獲美 國藥物管理局（FDA）認證。 According to a national cross-sectional study published in 2020, the prevalence of dementia among people aged 60 and over in China is 6 per cent, with Alzheimer’s disease (AD) patients accounting for 3.9 per cent. In other words, there are 15.07 million people aged 60 and over in China who have dementia, of which 9.83 million are AD patients. As China’s population ages, the social and economic burden of AD will continue to increase. Despite the rising incidence, the development of AD drugs has been unsuccessful for decades. Although leading pharmaceutical companies invested more than USD 600 billion in AD research and drug development between 2000 and 2017, most of the drug developments have failed due to the unknown pathological mechanism of AD. Mitophagy: A New Strategy to Treat Alzheimer’s Disease During the neuronal ageing process, damage to mitochondria, the ‘power plants’ within the cells, continue to accumulate, increasing the death of nerve cells. To ensure that mitochondria are in good condition, cells use mitophagy, a sophisticated quality control system, to selectively remove damaged mitochondria to maintain neuronal health. In our preliminary study, we found that damage to this system is key to the pathogenesis of AD. We have also found that stimulating mitochondrial phagocytosis can improve the pathology of animal models of AD and thus may be a promising new approach for the treatment of AD. 以人工智能技術篩選阿爾茨海默病潛在藥物並作多物種分析的流程 The workflow of an AI-based virtual screening and cross-species analysis for the discovery of AD drugs 2021 UMAGAZINE 24
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