Cysteinyl Leukotrienes and Their Receptors: Emerging Therapeutic Targets in Central Nervous System Disorders

Abstract

Cysteinyl leukotrienes are a group of the inflammatory lipid molecules well known as mediators of inflammatory signaling in the allergic diseases. Although they are traditionally known for their role in allergic asthma, allergic rhinitis, and others, recent advances in the field of biomedical research highlighted the role of these inflammatory mediators in a broader range of diseases such as in the inflammation associated with the central nervous system (CNS) disorders, vascular inflammation (atherosclerotic), and in cancer. Among the CNS diseases, they, along with their synthesis precursor enzyme 5-lipoxygenase and their receptors, have been shown to be associated with brain injury, Multiple sclerosis, Alzheimer's disease, Parkinson's disease, brain ischemia, epilepsy, and others. However, a lot more remains elusive as the research in these areas is emerging and only a little has been discovered. Herein, through this review, we first provided a general up-to-date information on the synthesis pathway and the receptors for the molecules. Next, we summarized the current findings on their role in the brain disorders, with an insight given to the future perspectives.

Hippocampal CysLT1R knockdown or blockade represses LPS-induced depressive behaviors and neuroinflammatory response in mice

“…Increasing evidence indicates a close link between neuroinflammation and depression, which is manifested by elevated levels of pro-inflammatory cytokines and chemokines in the central nervous system [29][30][31][32] . We previously identified CysLT 1 R signaling as a novel pro-inflammatory pathway in mice and suggested it as a potential therapeutic target for depression [18] .…”

GPR17 mediates ischemia-like neuronal injury via microglial activation

“…On the other hand, cysteinyl leukotrienes (CysLTs), including LTC 4 , LTD 4 and LTE 4 , are potent proinflammatory mediators. CysLTs are implicated in diverse pathologies, such as respiratory diseases, and inflammatory conditions, including cardiovascular, gastrointestinal, and immune disorders, as well as neurodegenerative responses, which are mediated by CysLT receptor 1 and CysLT receptor 2 ( 3 - 7 ). Both nucleotides and CysLTs are proven inducers of brain inflammation, and have important roles in ischemic/inflammatory conditions and neurodegenerative responses ( 2 , 7 ).…”

Neuropsychiatric Events Associated with Leukotriene-Modifying Agents: A Systematic Review

“…Conversely, several animal studies were conducted to investigate the therapeutic effect of LTMAs on Alzheimer's disease [50][51][52][53]. Leukotriene is involved in the inflammation in the brain and CysLT1 is found in the central nervous system [54]. Memory impairment was improved in animal models due to the reduction of neuroinflammation, a process potentially related to the progression of Alzheimer's disease [50][51][52][53].…”