Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Neurobiology of Disease Année : 2021

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

Résumé

Parkinson'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.
Fichier principal
Vignette du fichier
1-s2.0-S096999612100005X-main.pdf (10.89 Mo) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

hal-03195956 , version 1 (12-04-2021)

Identifiants

Citer

Antonio Dominguez-Meijide, Valeria Parrales, Eftychia Vasili, Florencia González-Lizárraga, Annekatrin König, et al.. Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo. Neurobiology of Disease, 2021, 151, pp.105256. ⟨10.1016/j.nbd.2021.105256⟩. ⟨hal-03195956⟩
115 Consultations
78 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More