Inflammatory role of S100A8/A9 in the central nervous system non-neoplastic diseases

S100A8 (MRP8) and S100A9 (MRP14) are critical mediators of the inflammatory response; they are usually present as heterodimers because of the instability of homodimers. Studies have demonstrated that S100A8/A9 expression is significantly upregulated in several central nervous system (CNS) diseases. S100A8/A9 is actively released by neutrophils and monocytes; it plays a key role in regulating the inflammatory response by stimulating leukocyte recruitment and inducing cytokine secretion during inflammation. Additionally, S100A8/A9 can be used as a diagnostic biomarker for several CNS diseases and as a predictor of therapeutic response to inflammation-related diseases. In this work, we reviewed our current understanding of S100A8/A9 overexpression in inflammation and its importance in the development and progression of CNS inflammatory diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and stroke, and the functional roles and therapeutic applications of S100A8/A9 in these diseases. Finally, we discussed the current barriers and future research directions of S100A8/A9 in CNS diseases.