Abstract
Neuroinflammation, which is mediated by microglia and astrocytes, is associated with the progression of neurodegenerative diseases. Increasing evidence shows that activated microglia induce the expression and secretion of various lysosomal cathepsins, particularly during the early stage of neuroinflammation. This trigger signaling cascade that aggravate neurodegeneration. To date, most research on neuroinflammation has focused on the role of cysteine cathepsins, the largest cathepsin family. Cysteine cathepsins are primarily responsible for protein degradation in lysosomes; however, they also play a role in regulating a number of other important physiological and pathological processes. This review focuses on the functional roles of cysteine cathepsins in the central nervous system during neuroinflammation, with an emphasis on their roles in the polarization of microglia and neuroinflammation signaling, which in turn causes neuronal death and thus neurodegeneration.
Highlights
Neuroinflammation is a common mechanism that plays a crucial role in the pathogenesis of various neurodegenerative diseases [1,2]
This review focuses on the functional roles of cysteine cathepsins in the central nervous system during neuroinflammation, with an emphasis on their roles in the polarization of microglia and neuroinflammation signaling, which in turn causes neuronal death and neurodegeneration
It is widely accepted that neuroinflammation is an important factor in the pathogenesis of several neurodegenerative diseases and that the process is driven by activated microglia, which release pro-inflammatory mediators into the neuronal environment
Summary
Neuroinflammation is a common mechanism that plays a crucial role in the pathogenesis of various neurodegenerative diseases [1,2]. It is a defense mechanism that protects the brain from diverse pathogens [3]. It may trigger both beneficial and detrimental effects on neurons [2,4,5]. In the CNS, microglia represent resident innate immune cells, and their contribution to inflammatory signaling pathways between neurons, astrocytes, and other components of brain tissue largely sets the magnitude of the immune response [16,17]. Increasing evidence shows that activated microglia express and secrete lysosomal cathepsins, during the early stage of neuroinflammation, which triggers signaling cascades that aggra vate neurodegeneration [26,27,28,29]. This review highlights new insights ofinto the roles of lysosomal peptidases, cysteine cathepsins during neuroinflammation
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