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Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo

Lookup NU author(s): Professor Tiago OuteiroORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).

Abstract

© 2021 The AuthorsParkinson's disease (PD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders characterized by the misfolding and aggregation of alpha-synuclein (aSyn). Doxycycline, a tetracyclic antibiotic shows neuroprotective effects, initially proposed to be due to its anti-inflammatory properties. More recently, an additional mechanism by which doxycycline may exert its neuroprotective effects has been proposed as it has been shown that it inhibits amyloid aggregation. Here, we studied the effects of doxycycline on aSyn aggregation in vivo, in vitro and in a cell free system using real-time quaking induced conversion (RT-QuiC). Using H4, SH-SY5Y and HEK293 cells, we found that doxycycline decreases the number and size of aSyn aggregates in cells. In addition, doxycycline inhibits the aggregation and seeding of recombinant aSyn, and attenuates the production of mitochondrial-derived reactive oxygen species. Finally, we found that doxycycline induces a cellular redistribution of aggregates in a C.elegans animal model of PD, an effect that is associated with a recovery of dopaminergic function. In summary, we provide strong evidence that doxycycline treatment may be an effective strategy against synucleinopathies.

Publication metadata

Author(s): Dominguez-Meijide A, Parrales V, Vasili E, Gonzalez-Lizarraga F, Konig A, Lazaro DF, Lannuzel A, Haik S, Del Bel E, Chehin R, Raisman-Vozari R, Michel PP, Bizat N, Outeiro TF

Publication type: Article

Publication status: Published

Journal: Neurobiology of Disease

Year: 2021

Volume: 151

Online publication date: 08/01/2021

Acceptance date: 06/01/2021

Date deposited: 19/03/2021

ISSN (print): 0969-9961

ISSN (electronic): 1095-953X

Publisher: Academic Press Inc.

URL: https://doi.org/10.1016/j.nbd.2021.105256

DOI: 10.1016/j.nbd.2021.105256

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