Artículo
Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo
Dominguez Meijide, Antonio; Parrales, Valeria; Vasili, Eftychia; González Lizarraga, Maria Florencia
; König, Annekatrin; Lázaro, Diana F.; Lannuzel, Annie; Haik, Stéphane; del Bel Belluz Guimaraes, Elaine; Chehin, Rosana Nieves
; Raisman Vozari, Rita; Michel, Patrick P.; Bizat, Nicolas; Outeiro, Tiago Fleming
Fecha de publicación:
04/2021
Editorial:
Academic Press Inc Elsevier Science
Revista:
Neurobiology of Disease
ISSN:
0969-9961
e-ISSN:
1095-953X
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
AGGREGATION
,
ALPHA-SYNUCLEIN
,
C. ELEGANS
,
DOXYCYCLINE
,
PARKINSON'S DISEASE
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos (IMMCA)
Articulos de INSTITUTO DE INVESTIGACIONES EN MEDICINA MOLECULAR Y CELULAR APLICADA DEL BICENTENARIO
Articulos de INSTITUTO DE INVESTIGACIONES EN MEDICINA MOLECULAR Y CELULAR APLICADA DEL BICENTENARIO
Citación
Dominguez Meijide, Antonio; Parrales, Valeria; Vasili, Eftychia; González Lizarraga, Maria Florencia; König, Annekatrin; et al.; Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo; Academic Press Inc Elsevier Science; Neurobiology of Disease; 151; 4-2021; 1-19
Compartir
Altmétricas