montelukast and Memory-Disorders

montelukast has been researched along with Memory-Disorders* in 2 studies

Other Studies

2 other study(ies) available for montelukast and Memory-Disorders

ArticleYear
The Leukotriene Receptor Antagonist Montelukast Reduces Alpha-Synuclein Load and Restores Memory in an Animal Model of Dementia with Lewy Bodies.
    Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2020, Volume: 17, Issue:3

    Dementia with Lewy bodies (DLB) represents a huge medical need as it accounts for up to 30% of all dementia cases, and there is no cure available. The underyling spectrum of pathology is complex and creates a challenge for targeted molecular therapies. We here tested the hypothesis that leukotrienes are involved in the pathology of DLB and that blocking leukotrienes through Montelukast, a leukotriene receptor antagonist and approved anti-asthmatic drug, might alleviate pathology and restore cognitive functions. Expression of 5-lipoxygenase, the rate-limiting enzyme for leukotriene production, was indeed elevated in brains with DLB. Treatment of cognitively deficient human alpha-synuclein overexpressing transgenic mice with Montelukast restored memory. Montelukast treatment resulted in modulation of beclin-1 expression, a marker for autophagy, and in a reduction in the human alpha-synulcein load in the transgenic mice. Reducing the protein aggregation load in neurodegenerative diseases might be a novel model of action of Montelukast. Moreover, this work presents leukotriene signaling as a potential drug target for DLB and shows that Montelukast might be a promising drug candidate for future DLB therapy development.

    Topics: Acetates; alpha-Synuclein; Animals; Cyclopropanes; Disease Models, Animal; Female; Humans; Leukotriene Antagonists; Lewy Body Disease; Memory; Memory Disorders; Mice; Mice, Transgenic; Quinolines; Receptors, Leukotriene; Sulfides

2020
Montelukast targeting the cysteinyl leukotriene receptor 1 ameliorates Aβ1-42-induced memory impairment and neuroinflammatory and apoptotic responses in mice.
    Neuropharmacology, 2014, Volume: 79

    Montelukast, known as a cysteinyl leukotriene receptor 1 (CysLT1R) antagonist, is currently used for treatment of inflammatory diseases such as asthma. Here, we investigated effects of montelukast on neuroinflammatory, apoptotic responses, and memory performance following intracerebral infusions of amyloid-β (Aβ). The data demonstrated that intracerebroventrical infusions of aggregated Aβ1-42 (410 pmol/mouse) produced deficits in learning ability and memory, as evidenced by increase in escape latency during acquisition trials and decreases in exploratory activities in the probe trial in Morris water maze (MWM) task, and by decrease in the number of correct choices and increase in latency to enter the shock-free compartment in Y-maze test, and caused significant increases in pro-inflammatory cytokines such as NF-κB p65, TNF-α and IL-1β as well as pro-apoptotic molecule caspase-3 activation and anti-apoptotic protein Bcl-2 downregulation in hippocampus and cortex. Interestingly, this treatment resulted in upregulation of protein or mRNA of CysLT1R in both hippocampus and cortex. Blockade of CysLT1R by repeated treatment with montelukast (1 or 2 mg/kg, ig, 4 weeks) reduced Aβ1-42-induced CysLT1R expression and also suppressed Aβ1-42-induced increments of NF-κB p65, TNF-α, IL-1β and caspase-3 activation, and Bcl-2 downregulation in the hippocampus and cortex. Correspondingly, montelukast treatment significantly improved Aβ1-42-induced memory impairment in mice, but had little effect on normal mice. Our results show that montelukast may ameliorate Aβ1-42-induced memory impairment via inhibiting neuroinflammation and apoptosis mediated by CysLT1R signaling, suggesting that CysLT1R antagonism represents a novel treatment strategy for Alzheimer's disease.

    Topics: Acetates; Amyloid beta-Peptides; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Caspase 3; Cerebral Cortex; Cyclopropanes; Cytokines; Hippocampus; Leukotriene Antagonists; Male; Maze Learning; Memory Disorders; Mice; Mice, Inbred ICR; Neuroprotective Agents; NF-kappa B; Nootropic Agents; Peptide Fragments; Proto-Oncogene Proteins c-bcl-2; Quinolines; Receptors, Leukotriene; Sulfides

2014