Kochman Urszula, Sitka Hanna, Kuźniar Julia, Czaja Magdalena, Kozubek Patrycja, Beszłej Jan Aleksander, Leszek Jerzy
Student Scientific Group of Psychiatry, Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland.
Department of Psychiatry, Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland.
Cells. 2025 Aug 30;14(17):1356. doi: 10.3390/cells14171356.
Alzheimer's disease (AD) is marked by the pathological aggregation of amyloid β (Aβ) and tau proteins. Emerging research reveals that these proteins undergo liquid-liquid phase separation (LLPS), forming biomolecular condensates that promote aggregation and neurotoxicity. These phase-separated structures reshape the intracellular environment, facilitating protein misfolding and spreading. This review highlights recent advances in understanding the role of condensates in AD pathogenesis and explores novel therapeutic strategies targeting condensate dynamics. Promising approaches include small molecules that disrupt LLPS, epigenetic drugs influencing nuclear condensates, and compounds like DDL 920 and RI AG03 that modulate tau phase separation and neuroinflammation, respectively. Additionally, anti-inflammatory agents, such as nucleotide reverse transcriptase inhibitors (NRTIs), offer potential for upstream intervention. Targeting biomolecular condensates presents a next-generation strategy for AD treatment. Future research should focus on in vivo profiling of condensate composition, biomarker development, and the development of patient-specific therapies to enable early, disease-modifying interventions.
阿尔茨海默病（AD）的特征是淀粉样β蛋白（Aβ）和tau蛋白的病理性聚集。新出现的研究表明，这些蛋白质会经历液-液相分离（LLPS），形成促进聚集和神经毒性的生物分子凝聚物。这些相分离结构重塑细胞内环境，促进蛋白质错误折叠和扩散。本综述重点介绍了在理解凝聚物在AD发病机制中的作用方面的最新进展，并探索了针对凝聚物动态变化的新型治疗策略。有前景的方法包括破坏LLPS的小分子、影响核凝聚物的表观遗传药物，以及分别调节tau相分离和神经炎症的DDL 920和RI AG03等化合物。此外，抗炎剂，如核苷酸逆转录酶抑制剂（NRTIs），提供了上游干预的潜力。靶向生物分子凝聚物是AD治疗的下一代策略。未来的研究应集中在凝聚物组成的体内分析、生物标志物的开发，以及针对患者的特异性疗法的开发，以实现早期的疾病修饰干预。
