montelukast and Parkinson-Disease

Parkinson's disease (PD) is a neurodegenerative disorder where misfolded alpha-synuclein-enriched aggregates called Lewy bodies are central in pathogenesis. No neuroprotective or disease-modifying treatments are currently available. Parkinson's disease is considered a multifactorial disease and evidence from multiple patient studies and animal models has shown a significant immune component during the course of the disease, highlighting immunomodulation as a potential treatment strategy. The immune changes occur centrally, involving microglia and astrocytes but also peripherally with changes to the innate and adaptive immune system. Here, we review current understanding of different components of the PD immune response with a particular emphasis on the leukotriene pathway. We will also describe evidence of montelukast, a leukotriene receptor antagonist, as a possible anti-inflammatory treatment for PD.

Topics: Acetates; Anti-Inflammatory Agents; Astrocytes; Cyclopropanes; Humans; Inflammation; Leukotriene Antagonists; Lewy Bodies; Microglia; Parkinson Disease; Quinolines; Receptors, Leukotriene; Sulfides

This study was undertaken to examine the association between montelukast use, β2-adrenoreceptor (β2AR) agonist use, and later Parkinson disease (PD).. We ascertained use of β2AR agonists (430,885 individuals) and montelukast (23,315 individuals) from July 1, 2005 to June 30, 2007, and followed 5,186,886 PD-free individuals from July 1, 2007 to December 31, 2013 for incident PD diagnosis. We estimated hazard ratios and 95% confidence intervals using Cox regressions.. We observed 16,383 PD cases during on average 6.1 years of follow-up. Overall, use of β2AR agonists and montelukast were not related to PD incidence. A 38% lower PD incidence was noted among high-dose montelukast users when restricted to PD registered as the primary diagnosis.. Overall, our data do not support inverse associations between β2AR agonists, montelukast, and PD. The prospect of lower PD incidence with high-dose montelukast exposure warrants further investigation, especially with adjustment for high-quality data on smoking. ANN NEUROL 2023;93:1023-1028.

Topics: Acetates; Cyclopropanes; Humans; Parkinson Disease; Quinolines

Although the main cause of degeneration of the nigrostriatal dopaminergic (DA) projection in Parkinson's disease (PD) is still controversial, many reports suggest that excessive inflammatory responses mediated by activated microglia can induce neurotoxicity in the nigrostriatal DA system in vivo. Montelukast, which plays an anti-inflammatory role, is used to treat patients with asthma. In addition, recent studies have reported that its administration could reduce neuroinflammatory activities, showing beneficial effects against various neuropathological conditions. These results suggest that montelukast may be a useful drug to alleviate inflammatory responses in PD, even though there are no reports showing its beneficial effects against neurotoxicity in the nigrostriatal DA system. In the present study, our results showed that treatment with montelukast could protect DA neurons against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity and its administration significantly attenuated the production of neurotoxic cytokines such as tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) from activated microglia in the substantia nigra (SN) and striatum following 6-OHDA treatment. Therefore, we suggest that montelukast can be used as a potential inhibitor of microglial activation to protect DA neurons in the adult brain against PD.

Topics: Acetates; Adrenergic Agents; Animals; Calcium-Binding Proteins; Cyclopropanes; Cytokines; Disease Models, Animal; Dopaminergic Neurons; Dose-Response Relationship, Drug; Male; Mice; Mice, Inbred C57BL; Microfilament Proteins; Microglia; Neuroprotective Agents; Oxidopamine; Parkinson Disease; Quinolines; Rotarod Performance Test; Substantia Nigra; Sulfides; Tyrosine 3-Monooxygenase

Topics: Acetates; Aging; Alzheimer Disease; Animals; Anti-Asthmatic Agents; Cognition Disorders; Cyclopropanes; Estrogens; Female; Hippocampus; Humans; Inflammation Mediators; Leukotrienes; Macaca mulatta; Male; Mice; Neuronal Plasticity; Parkinson Disease; Plasma; Prefrontal Cortex; Quinolines; Rats; Rejuvenation; Sulfides; Synapses