Lysosomal modifications in astrocytes exposed to pathological α‐synuclein

In summary, our findings reveal that fibrillar αS induces significant, time-dependent changes in lysosomal enzyme activity and protein expression in astrocytes across multiple cellular models. We demonstrate that astrocytes possess a remarkable capacity to manage pathological αS from exogenous sources. Moreover, our results highlight the dynamic resilience of astrocytic lysosomes in recovering from αS-induced dysfunction. These findings emphasize the critical role of lysosomal function in astrocytes and suggest that targeting the astrocytic lysosomal system could enhance the degradation of pathological αS, potentially mitigating neurodegeneration and improving clinical outcomes in DLB and other α-synucleinopathies.