RT Journal Article
T1 Doxycycline inhibits α-synuclein-associated pathologies in vitro and in vivo
A1 Domínguez Meijide, Antonio
A1 Parrales, Valeria
A1 Vasili, Eftychia
A1 González Lizárraga, Florencia
A1 König, Annekatrin
A1 Lázaro, Diana F.
A1 Lannuzel, Annie
A1 Haik, Stéphane
A1 Del Bel, Elaine
A1 Chehín, Rosana
A1 Raisman Vozari, Rita
A1 Michel, Patrick P.
A1 Bizat, Nicolas
A1 Outeiro, Tiago Fleming
K1 Alpha-synuclein
K1 Parkinson's disease
K1 Doxycycline
K1 Aggregation
K1 C. elegans
AB 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
PB Elsevier
SN 0969-9961
YR 2021
FD 2021
LK http://hdl.handle.net/10347/24391
UL http://hdl.handle.net/10347/24391
LA eng
NO Neurobiology of Disease, Volume 151, April 2021, 105256
DS Minerva
RD 1 may 2026