Minocycline and cytoprotection: shedding new light on a shadowy controversy.
In this review we explore and integrate the knowledge of the plausible pharmacological targets that could explain the new application for the well known semi-synthetic, tetracycline-derivate minocycline as a cytoprotective drug. In doing so, we will analyze the possible mechanisms to elucidate the potential cytoprotective properties of minocycline. We address its anti-oxidant action ranging from its structure to its capacity to modulate the expression of oxidant-related enzymes such as nitric oxide synthase. The pharmacological targets responsible for its anti-inflammatory effects are surveyed. The effects of this antibiotic are making its marks on intracellular pathways related to neurodegenerative processes such as mitochondrially-mediated apoptosis, including minocycline-modulated effects on the expression of apoptotic proteins. Finally, we will explore the effects of minocycline on metalloproteinases, enzymes implicated in the modulation of cerebrovascular post-ischemic oxidative reperfusion injury, and new targets. In conclusion, we shed new light on the shadowy controversy of minocycline's potential cytoprotective mechanisms and targets of action.
Jordan
J
J
Grupo de Neurofarmacología, Departamento de Ciencias Médicas, Facultad de Medicina, Universidad de Castilla-La Mancha, Albacete, Spain. joaquin.jordan@uclm.es
Fernandez-Gomez
F J
FJ
Ramos
M
M
Ikuta
I
I
Aguirre
N
N
Galindo
M F
MF
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019610:Cytoprotection; D016503:Drug Delivery Systems; D006801:Humans; D045726:Metalloproteases / Q000187:drug effects; D008911:Minocycline / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D019001:Nitric Oxide Synthase / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000975:Antioxidants; D019001:Nitric Oxide Synthase; D045726:Metalloproteases; D008911:Minocycline