Montelukast targeting the cysteinyl leukotriene receptor 1 ameliorates Aβ1-42-induced memory impairment and neuroinflammatory and apoptotic responses in mice

Lai, Jin’e; Meng, Heng; Wang, Hao; Mei, Hu; Long, Yan; Miao, Ming; Li, Jiachang; Wang, Xiaobing; Hong, Hao

doi:10.1016/j.neuropharm.2014.01.011

Cited by 81 publications

(56 citation statements)

References 52 publications

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“…Anti-inflammatory effects of the two test Opposite to results of oxidative parameters, ML showed more significant anti-inflammatory potential compared with LC. This is in harmony with recent investigations declaring potent antiinflammatory potential for ML 28,29 . Besides the well-known inhibitory Fortunately, the present study results showed that combination of ML with LC showed more significant protective effect than either drug alone regarding levels of tissue GSH, TBARS, GST, SOD and NO2 -, and levels of serum COX-II and LOX.…”

Section: Discussionsupporting

confidence: 90%

Protective Effects of Montelukast and L-Carnitine on Cyclophosphamide-Induced Lung Injury

Hassanein

Abo-Youssef

Messiha

et al. 2015

PBJ

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The major aim of this work was to study the protective effects of the cysteinyl-leukotriene antagonist montelukast (ML) and L-Carnitine (LC) against cyclophosphamide (CP)-induced pulmonary injury in experimental rats. Thirty adult male albino rats were categorized at random into five groups of 6 rats each. The first group served as normal control group. All other groups were injected once with CP (150 mg/kg, i.p.). The second group was kept as CP toxicity control group The third group was injected with ML (10 mg/kg/day, i.

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Section: Discussionsupporting

confidence: 90%

Protective Effects of Montelukast and L-Carnitine on Cyclophosphamide-Induced Lung Injury

Hassanein

Abo-Youssef

Messiha

et al. 2015

PBJ

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“…However, the zymogen feature of caspase-3 is necessary because if unregulated,caspase activity would kill cells indiscriminately [41]. It has been reported that caspase-3 is a predominant target involved in PIC-mediated apoptosis in neuronal cells during αβ 1-42 -induced memory impairment [42]. Thus, in the current study, we also determined the protein expression levels of a cleaved form caspase-3 in the hippocampal tissues as an indicator of cellular apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer’s disease rats

Wang

et al. 2016

Translational Neuroscience

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As a part of Alzheimer’s disease (AD) development the mammalian target of rapamycin (mTOR) has been reported to play a crucial role in regulating cognition and can be used as a neuronal marker. Neuro-inflammation is also a cause of the pathophysiological process in AD. Thus, we examined the protein expression levels of mTOR and its downstream pathways as well as pro-inflammatory cytokines (PICs) in the brain of AD rats. We further examined the effects of blocking mTOR on PICs, namely IL-1β, IL-6 and TNF-α. Our results showed that the protein expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in the hippocampus of AD rats compared with controls. Blocking mTOR by using rapamycin selectively enhanced activities of IL-6 and TNF-α signaling pathways, which was accompanied with an increase of Caspase-3, indicating cellular apoptosis and worsened learning performance. In conclusion, our data for the first time revealed specific signaling pathways engaged in the development of AD, including a regulatory role by the activation of mTOR in PIC mechanisms. Stimulation of mTOR is likely to play a beneficial role in modulating neurological deficits in AD.Targeting one or more of these signaling molecules may present with new opportunities for treatment and clinical management of AD

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“…Furthermore, in vivo and in vitro studies showed that LTD4-induced upregulation of CysLTR-1 is correlated with increased A β and amyloid precursor protein (APP) and with cognitive dysfunctions in mice [122–124]. In parallel, the microinfusion of A β 1–42 , a more neurotoxic A β species, resulted in significant increase in CysLT1-R expression in the hippocampus and cortex [125]. …”

Section: Cerebral Localization Of Cyslt Receptorsmentioning

confidence: 99%

“…In bilateral i.c.v. A β 1–42 -injected mice, pranlukast and montelukast reversed the A β 1–42 -induced cognitive deficits associated to inflammatory and apoptotic responses, as evidenced by decreased NF-kB p65, TNF- α , IL-1 β , and caspase-3 in the hippocampus and cortex [125, 132]. Moreover, in other studies, montelukast restores learning and memory function in old rats, in which cognition is compromised and the hippocampus concentrations of 5-LOX transcripts and of leukotrienes were increased [27, 133].…”

Section: Cerebral Localization Of Cyslt Receptorsmentioning

confidence: 99%

Cysteinyl Leukotrienes as Potential Pharmacological Targets for Cerebral Diseases

Gelosa

Colazzo

Tremoli

et al. 2017

Mediators of Inflammation

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Cysteinyl leukotrienes (CysLTs) are potent lipid mediators widely known for their actions in asthma and in allergic rhinitis. Accumulating data highlights their involvement in a broader range of inflammation-associated diseases such as cancer, atopic dermatitis, rheumatoid arthritis, and cardiovascular diseases. The reported elevated levels of CysLTs in acute and chronic brain lesions, the association between the genetic polymorphisms in the LTs biosynthesis pathways and the risk of cerebral pathological events, and the evidence from animal models link also CysLTs and brain diseases. This review will give an overview of how far research has gone into the evaluation of the role of CysLTs in the most prevalent neurodegenerative disorders (ischemia, Alzheimer's and Parkinson's diseases, multiple sclerosis/experimental autoimmune encephalomyelitis, and epilepsy) in order to understand the underlying mechanism by which they might be central in the disease progression.

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Montelukast targeting the cysteinyl leukotriene receptor 1 ameliorates Aβ1-42-induced memory impairment and neuroinflammatory and apoptotic responses in mice

Cited by 81 publications

References 52 publications

Protective Effects of Montelukast and L-Carnitine on Cyclophosphamide-Induced Lung Injury

Protective Effects of Montelukast and L-Carnitine on Cyclophosphamide-Induced Lung Injury

Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer’s disease rats

Cysteinyl Leukotrienes as Potential Pharmacological Targets for Cerebral Diseases

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