Cysteine leukotrienes as key mediators of immune-dependent diseases and the therapeutic potential of the leukotriene receptor antagonist (montelukast). Part 1

Background. Cysteine leukotrienes are lipid mediators formed upon activation of the 5-lipoxygenase pathway of arachidonate metabolism. These are universal mediators with a wide spectrum of action, affecting almost all aspects of mammalian biology. In clinical allergy and immunology they are best known for their role in the formation of immune-related diseases of the upper and lower respiratory tract.

Results. A brief history of their discovery and study of the role of leukotriene receptor antagonists (montelukast and its analogs), identification of their therapeutic effect and possible undesirable effects are an important illustration for understanding the inclusion of montelukast in national, international clinical guidelines and consensuses. Montelukast is a cysteinyl-leukotriene receptor 1 antagonist, inhibits the effects of leukotrienes and is widely used for the treatment of asthma and allergic rhinitis; it is included in the clinical guidelines for the treatment of these diseases. The drug interferes with molecular signalling pathways produced by leukotrienes in various cells and tissues of the human body. In recent years, a new therapeutic strategy has been observed – repositioning of existing drugs. The anti-inflammatory effects of montelukast are not limited to the respiratory system, but are more systemic in nature, which has led to the development of clinical studies aimed at the reuse of montelukast for the treatment of various inflammatory conditions, particularly for the treatment of several neurodegenerative diseases. Recent advances in neuroinflammation research have led to the discovery of several novel inflammatory pathways regulating many cerebral pathologies. Through pharmacological and genetic studies, cysteinyl leukotriene receptors have been shown to be involved in the pathogenesis of Alzheimer's disease and other neurodegenerative/neurological diseases such as Parkinson's disease, multiple sclerosis and epilepsy. This updated review will also highlight research into the therapeutic potential of montelukast beyond clinical guidelines for rhinitis and asthma.