Krembil Research Institute, University Health Network, Departments of Medicine, Chemistry and Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5T 0S8, Canada.
Curr Alzheimer Res. 2024;20(12):821-826. doi: 10.2174/0115672050301583240307114452.
There shall probably be no "magic bullet" for Alzheimer's; rather, we should be pursuing a "magic shotgun blast" that will target multiple complementary therapeutic receptors. Although protein misfolding/oligomerization will probably be one of these targets, this alone is insufficient and will require the co-administration of other therapeutic entities engaging targets, such as immunopathy, gliopathy, mitochondriopathy, synaptotoxicity or others. Although polypharmacy is emerging as the preferred therapeutic route, many questions remain unanswered. Should this be a cocktail of biologics, a concoction of small molecules, or a judicious combination of both? Biologics and small molecule drugs display both strengths and weaknesses. When addressing a disease as complex and globally important as Alzheimer's, there should be room for the continuing development of both of these therapeutic classes. Each has much to offer, and when used with their advantages and disadvantages in clear focus, an ultimate solution will probably require contributions from both.
治疗阿尔茨海默病可能不会有“灵丹妙药”；相反，我们应该追求一种“万能霰弹枪式的打击”，针对多个互补的治疗靶点。虽然蛋白错误折叠/寡聚化可能是这些靶点之一，但这还远远不够，还需要联合其他治疗实体来靶向这些靶点，如免疫病理、神经胶质病理、线粒体病理、突触毒性或其他病理。虽然联合用药正在成为首选的治疗途径，但仍有许多问题尚未得到解答。这应该是生物制剂的鸡尾酒疗法，还是小分子药物的混合物，或者是两者的合理组合？生物制剂和小分子药物都有其优缺点。在解决像阿尔茨海默病这样复杂且全球重要的疾病时，这两种治疗药物类别都应该有继续发展的空间。它们都有各自的优势，如果能明确关注其优缺点，那么最终的解决方案可能需要两者共同贡献。
