Modulation of neuroinflammation by cysteinyl leukotriene 1 and 2 receptors: Implications for cerebral ischemia and neurodegenerative diseases

Abstract Neuroinflammation is a complex biological process and has been known to play an important role in age-related cerebrovascular and neurodegenerative disorders, such as cerebral ischemia, Alzheimer's disease (AD) and Parkinson's disease (PD). Cysteinyl leukotrienes (CysLTs) are potent inflammatory lipid mediators that exhibit actions mainly through activating type 1 and type 2 CysLT receptors (CysLT1 and CysLT2). Accumulating evidence shows that CysLT1 and CysLT2 are activated at different stages of pathological process in various cell types in the brain such as vascular endothelial cells, astrocytes, microglia and neurons in response to insults. However, the precise roles and mechanisms of CysLT1 and CysLT2 in regulating the pathogenesis of cerebral ischemia, AD and PD are not fully understood. In this article, we focus on current advances that link activation of CysLT1 and CysLT2 to the pathological process during brain ischemia and neurodegeneration, and discuss mechanisms by which CysLT1 and CysLT2 mediate inflammatory process and brain injury. Multitarget antiinflammatory potentials of CysLT1 and CysLT2 antagonism for neuroinflammation and brain injury will also be reviewed.