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The Leukotriene Receptor Antagonist Montelukast Reduces Alpha-Synuclein Load and Restores Memory in an Animal Model of Dementia with Lewy Bodies

Lookup NU author(s): Mary Johnson, Professor Johannes AttemsORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2020, The Author(s). 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.

Publication metadata

Author(s): Marschallinger J, Altendorfer B, Rockenstein E, Holztrattner M, Garnweidner-Raith J, Pillichshammer N, Leister I, Hutter-Paier B, Strempfl K, Unger MS, Chishty M, Felder T, Johnson M, Attems J, Masliah E, Aigner L

Publication type: Article

Publication status: Published

Journal: Neurotherapeutics

Year: 2020

Volume: 17

Pages: 1061-1074

Print publication date: 01/07/2020

Online publication date: 18/02/2020

Acceptance date: 02/04/2018

Date deposited: 02/03/2020

ISSN (print): 1933-7213

ISSN (electronic): 1878-7479

Publisher: Springer Nature

URL: https://doi.org/10.1007/s13311-020-00836-3

DOI: 10.1007/s13311-020-00836-3

PubMed id: 32072462

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