A novel therapeutic potential of cysteinyl leukotrienes and their receptors modulation in the neurological complications associated with Alzheimer's disease

Abstract

Cysteinyl leukotrienes (cysLTs) are member of eicosanoid inflammatory lipid mediators family produced by oxidation of arachidonic acid by action of the enzyme 5-lipoxygenase (5-LOX). 5-LOX is activated by enzyme 5-Lipoxygenase-activating protein (FLAP), which further lead to production of cysLTs i.e. leukotriene C4 (LTC4), leukotriene D4 (LTD4) and leukotriene E4 (LTE4). CysLTs then produce their potent inflammatory actions by activating CysLT1 and CysLT2 receptors. Inhibitors of cysLTs are indicated in asthma, allergic rhinitis and other inflammatory disorders. Earlier studies have associated cysLTs and their receptors in several neurodegenerative disorders diseases like, multiple sclerosis, Parkinson's disease, Huntington's disease, epilepsy and Alzheimer's disease (AD). These inflammatory lipid mediators have previously shown effects on various aggravating factors of AD. However, not much data has been elucidated to test their role against AD clinically. Herein, through this review, we have provided the current and emerging information on the role of cysLTs and their receptors in various neurological complications responsible for the development of AD. In addition, literature evidences for the effect of cysLT inhibitors on distinct aspects of abnormalities in AD has also been reviewed. Promising advancement in understanding on the role of cysLTs on the various neuromodulatory processes and mechanisms may contribute to the development of newer and safer therapy for the treatment of AD in future.

Keywords: 5-lipoxygenase; Alzheimer's disease; Cysteinyl leukotrienes; HAMI 3379; Montelukast; Pranlukast.