Minocycline and Cytoprotection: Shedding New Light on a Shadowy Controversy

J. Jordan; F.J. Fernandez-Gomez; M. Ramos; I. Ikuta; N. Aguirre; M.F. Galindo

Abstract

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 minocyclines potential cytoprotective mechanisms and targets of action.

Keywords: Anti-inflammatory, anti-oxidant, apoptosis, cytoprotection, minocycline, mitochondria, modulation of the expression of anti-apoptotic proteins, reactive oxygen species