Jeon, Minsol Kim, Da-Eun Choi, So Young Kim, Seoyoung Seongchan, Kim LEE, HYO JIN Kim, Hyunkyung 2025-07-18T09:01:37Z 2025-07-18T09:01:37Z 2025-07-18 2025-06 1478-811X https://pubs.kist.re.kr/handle/201004/152826 The autophagy-lysosomal pathway is a cellular degradation mechanism that regulates protein quality by eliminating aggregates and maintaining normal protein function. It has been reported that aging itself reduces lysosomal proteolytic activity in age-related neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Reduction in lysosomal function may underlie the accumulation of protein aggregates such as amyloid beta (A beta), tau, and alpha-synuclein. Some of these protein aggregates may cause additional lysosomal dysfunction and create a vicious cycle leading to a gradual increase in protein aggregation. In this study, liposome-based lysosomal pH-modulating particles (LPPs), containing a liquid solution to adjust lysosomal pH, have been developed to restore lysosomal function. The results demonstrate that acidic LPPs effectively restore lysosomal function by recovering lysosomal pH and facilitating the removal of protein aggregates. These findings demonstrated that acidic LPPs could effectively recover the abnormal lysosomal function via restoration of lysosomal pH and enhance the clearance of protein aggregates. Furthermore, the simultaneous introduction of Cathepsin B (CTSB) proteins and acidic LPP revealed a synergistic effect, promoting lysosomal pH recovery and enhancing aggregates removal. These findings suggest a novel strategy for improving lysosomal clearance activity in proteinopathies. English BioMed Central Lysosomal targeting of liposomes with acidic pH and Cathepsin B induces protein aggregate clearance Article 10.1186/s12964-025-02310-z 1 Cell Communication and Signaling, v.23 Cell Communication and Signaling 23 Y scie scopus 001512039000001 Cell Biology Cell Biology Article DRUG-DELIVERY OXIDATIVE STRESS INCLUSION-BODIES AUTOPHAGY DISEASE BETA DYSFUNCTION HUNTINGTIN SYSTEMS Lysosome Aggregate clearance Cathepsin Autophagy Proteinopathy