Lysosomal
peptidases are hydrolytic
enzymes capable of digesting waste
proteins that are targeted to lysosomes via endocytosis and autophagy. Besides intracellular
protein catabolism, they play more specific roles in several other cellular processes and pathologies, either within lysosomes, upon secretion into the cell cytoplasm or extracellular space, or bound to the plasma membrane. In
cancer, lysosomal
peptidases are generally associated with
disease progression, as they participate in crucial processes leading to changes in cell morphology, signaling, migration, and invasion, and finally
metastasis. However, they can also enhance the mechanisms resulting in
cancer regression, such as apoptosis of
tumor cells or antitumor immune responses. Lysosomal
peptidases have also been identified as hallmarks of aging and neurodegeneration, playing roles in oxidative stress,
mitochondrial dysfunction, abnormal intercellular communication, dysregulated trafficking, and the deposition of
protein aggregates in neuronal cells. Furthermore, deficiencies in lysosomal
peptidases may result in other pathological states, such as
lysosomal storage disease. The aim of this review was to highlight the role of lysosomal
peptidases in particular
pathological processes of
cancer and neurodegeneration and to address the potential of lysosomal
peptidases in diagnosing and treating patients.