School of Pharmacy and Medical Sciences, Griffith University, Queensland, 4222, Australia.
School of Pharmacy and Medical Sciences, Griffith University, Queensland, 4222, Australia; Institute for Glycomics, Griffith University, Queensland, 4222, Australia.
Eur J Pharmacol. 2024 Sep 5;978:176755. doi: 10.1016/j.ejphar.2024.176755. Epub 2024 Jun 21.
Cysteinyl leukotrienes (CysLTs) are central to the pathophysiology of asthma and various inflammatory disorders. Leukotriene receptor antagonists (LTRAs) effectively treat respiratory conditions by targeting cysteinyl leukotriene receptors, CysLT and CysLT subtypes. This review explores the multifaceted effects of LTs, extending beyond bronchoconstriction. CysLT receptors are not only present in the respiratory system but are also crucial in neuronal signaling pathways. LTRAs modulate these receptors, influencing downstream signaling, calcium levels, inflammation, and oxidative stress (OS) within neurons hinting at broader implications. Recent studies identify novel molecular targets, sparking interest in repurposing LTRAs for therapeutic use. Clinical trials are investigating their potential in neuroinflammation control, particularly in Alzheimer's disease (AD) and Parkinson's diseases (PD). However, montelukast, a long-standing LTRA since 1998, raises concerns due to neuropsychiatric adverse drug reactions (ADRs). Despite widespread use, understanding montelukast's metabolism and underlying ADR mechanisms remains limited. This review comprehensively examines LTRAs' diverse biological effects, emphasizing non-bronchoconstrictive activities. It also analyses plausible mechanisms behind LTRAs' neuronal effects, offering insights into their potential as neurodegenerative disease modulators. The aim is to inform clinicians, researchers, and pharmaceutical developers about LTRAs' expanding roles, particularly in neuroinflammation control and their promising repurposing for neurodegenerative disease management.
半胱氨酰白三烯（CysLTs）在哮喘和各种炎症性疾病的病理生理学中起着核心作用。白三烯受体拮抗剂（LTRAs）通过靶向半胱氨酰白三烯受体（CysLT 和 CysLT 亚型），有效地治疗呼吸系统疾病。本文探讨了 LT 的多方面作用，这些作用不仅限于支气管收缩。CysLT 受体不仅存在于呼吸系统中，而且在神经元信号通路中也起着至关重要的作用。LTRAs 调节这些受体，影响下游信号、钙水平、炎症和神经元中的氧化应激（OS），暗示着更广泛的影响。最近的研究确定了新的分子靶点，激发了重新利用 LTRAs 进行治疗的兴趣。临床试验正在研究它们在神经炎症控制中的潜在作用，特别是在阿尔茨海默病（AD）和帕金森病（PD）中。然而，孟鲁司特作为一种自 1998 年以来长期使用的 LTRA，由于神经精神不良药物反应（ADR）而引起关注。尽管广泛使用，但对孟鲁司特的代谢和潜在 ADR 机制的了解仍然有限。本文全面检查了 LTRAs 的多种生物学作用，强调了非支气管收缩活性。它还分析了 LTRAs 对神经元影响的可能机制，为它们作为神经退行性疾病调节剂的潜在作用提供了见解。目的是向临床医生、研究人员和药物开发商通报 LTRAs 不断扩大的作用，特别是在神经炎症控制方面，以及它们在神经退行性疾病管理方面有前途的重新利用。
