Fig. 3

Factors affecting lysosomal acidification dysfunction in astrocytes. (A) Exposure to different cytokines triggers neuroinflammatory signaling that induce diverse astrocyte inflammatory phenotypes. Cytokines exposure leads to a reduction of lysosomal V-ATPase levels, leading to elevated lysosomal pH and reduced lysosomal enzyme degradative capacity. Chronic autolysosomal buildup due to incomplete degradation leads to exocytosis of neurotoxic factors which impair surrounding neurons. (B) Changes in nutrient levels induce metabolic stress which lead to mitochondrial dysfunction and impaired lysosomal acidification. (C) In astrocytes with lipids or myelin accumulation, lysosomal size is increased along with elevated lysosomal pH. In addition, high fat diet intake and metabolic disorders that affect the peripheral organs can also affect astrocyte function and reactivity. (D) Toxic proteins aggregates taken up by astrocytes localized into lysosomes and impaired lysosomal acidification, resulting in cellular dysfunction and spreading of pathology due to inefficient degradation and increased release of the toxic materials. The figure was created with BioRender.com