scholarly journals Effect of the leukotriene receptor antagonist ONO-1078 on extravascular lung water after coronary ligation in dogs.

1993 ◽  
Vol 57 (2) ◽  
pp. 161-166 ◽  
Author(s):  
HIROYA TANIGUCHI ◽  
YASUO TAKAYAMA ◽  
TOSHIJI IWASAKA ◽  
TERUHIRO TAMURA ◽  
HIROFUMI TAKASHIMA ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Extravascular Lung Water ◽  
Leukotriene Receptor Antagonist ◽  
Lung Water ◽  
Coronary Ligation ◽  
Leukotriene Receptor

Montelukast, a Leukotriene-Receptor Antagonist, for the Treatment of Mild Asthma and Exercise-Induced Bronchoconstriction

1999 ◽  
Vol 43 (3) ◽  
pp. 185-186
Author(s):  
JONATHAN A. LEFF ◽  
WILLIAM W. BUSSE ◽  
DAVID PEARLMAN ◽  
EDWIN A. BRONSKY ◽  
JAMES KEMP ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Mild Asthma ◽  
Leukotriene Receptor Antagonist ◽  
Leukotriene Receptor ◽  
Exercise Induced

scholarly journals The Leukotriene Receptor Antagonist Montelukast Attenuates Neuroinflammation and Affects Cognition in Transgenic 5xFAD Mice

2021 ◽  
Vol 22 (5) ◽  
pp. 2782 ◽  
Author(s):  
Johanna Michael ◽  
Julia Zirknitzer ◽  
Michael Stefan Unger ◽  
Rodolphe Poupardin ◽  
Tanja Rieß ◽  
...  
Keyword(s):  
T Cells ◽  
Receptor Antagonist ◽  
Cd8 T Cells ◽  
Disease Model ◽  
Cognitive Outcome ◽  
Drug Candidate ◽  
Potential Drug ◽  
Leukotriene Receptor Antagonist ◽  
Leukotriene Receptor ◽  
5Xfad Mice

Alzheimer’s disease (AD) is the most common form of dementia. In particular, neuroinflammation, mediated by microglia cells but also through CD8+ T-cells, actively contributes to disease pathology. Leukotrienes are involved in neuroinflammation and in the pathological hallmarks of AD. In consequence, leukotriene signaling—more specifically, the leukotriene receptors—has been recognized as a potential drug target to ameliorate AD pathology. Here, we analyzed the effects of the leukotriene receptor antagonist montelukast (MTK) on hippocampal gene expression in 5xFAD mice, a commonly used transgenic AD mouse model. We identified glial activation and neuroinflammation as the main pathways modulated by MTK. The treatment increased the number of Tmem119+ microglia and downregulated genes related to AD-associated microglia and to lipid droplet-accumulating microglia, suggesting that the MTK treatment targets and modulates microglia phenotypes in the disease model compared to the vehicle. MTK treatment further reduced infiltration of CD8+T-cells into the brain parenchyma. Finally, MTK treatment resulted in improved cognitive functions. In summary, we provide a proof of concept for MTK to be a potential drug candidate for AD and provide novel modes of action via modulation of microglia and CD8+ T-cells. Of note, 5xFAD females showed a more severe pathology, and in consequence, MTK treatment had a more pronounced effect in the females compared to the males. The effects on neuroinflammation, i.e., microglia and CD8+ T-cells, as well as the effects on cognitive outcome, were dose-dependent, therefore arguing for the use of higher doses of MTK in AD clinical trials compared to the approved asthma dose.

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