Minocycline, an antibiotic of the tetracycline family, has been shown to display neurorestorative or neuroprotective properties in various models of neurodegenerative diseases. In particular, it has been shown to delay motor alterations, inflammation and apoptosis in models of Huntington's disease, amyotrophic lateral sclerosis and Parkinson's disease. Despite controversies about its efficacy, the relative safety and tolerability of minocycline have led to various clinical trials. Recently, we reported the antipsychotic effects of minocycline in patients with schizophrenia. In a pilot investigation, we administered minocycline as an open-label adjunct to antipsychotic medication to patients with schizophrenia. The results of this trial suggested that minocycline might be a safe and effective adjunct to antipsychotic medications, and that augmentation with minocycline may prove to be a viable strategy for "boosting" antipsychotic efficacy and for treating schizophrenia. The present review summarizes the available data supporting the clinical testing of minocycline for patients with schizophrenia. In addition, we extend our discussion to the potential applications of minocycline for combining this treatment with cellular and molecular therapy.
"Pleiotropic properties of minocycline targeting multiple proteins and cellular processes implicated in the pathoetiology of mood disorders make it a suitable candidate for treatment of depression (Soczynska et al., 2012). It may be a valuable adjunctive therapeutic agent to antipsychotic medication in patients with schizophrenia as well (Miyaoka, 2008). In a clinical ad-on trial, minocycline treatment of early-phase schizophrenia patients improved negative symptoms and cognitive functions (Levkovitz et al., 2010). "
[Show abstract][Hide abstract] ABSTRACT: Biological functions of antibiotics are not limited to killing. The most likely function of antibiotics in natural microbial ecosystems is signaling. Does this signaling function of antibiotics also extend to the eukaryotic - in particular mammalian - cells? In this review, the host modulating properties of three classes of antibiotics (macrolides, tetracyclines, and β-lactams) will be briefly discussed. Antibiotics can be effective in treatment of a broad spectrum of diseases and pathological conditions other than those of infectious etiology and, in this capacity, may find widespread applications beyond the intended antimicrobial use. This use, however, should not compromise the primary function antibiotics are used for. The biological background for this inter-kingdom signaling is also discussed.
Frontiers in Microbiology 08/2013; 4:241. DOI:10.3389/fmicb.2013.00241 · 3.99 Impact Factor
"Minocycline, a brain-penetrable antibiotic (Fagan et al., 2004) is capable of modifying brain functioning in conditions ranging from neurodegeneration (Chu et al., 2010; Elewa et al., 2006; Li et al., 2009) to psychiatric disorders (Miyaoka et al., 2008; Neigh et al., 2009; Pae et al., 2008) and addiction (Chen et al., 2009; Habibi-Asl et al., 2009; Kofman et al., 1990; Sofuoglu et al., 2009). Some of these minocycline actions have been attributed to its ability to inhibit the 5-LOX pathway (Chu et al., 2007, 2010; Song et al., 2004, 2006). "
[Show abstract][Hide abstract] ABSTRACT: In wild-type (WT) mice, the antibiotic minocycline inhibits development of cocaine-induced locomotor sensitization. Some of the actions of minocycline may involve the 5-lipoxygenase (5-LOX) pathway. We used the model of 5-LOX-deficient mice to investigate whether 5-LOX participates in minocycline's influence on the effects of cocaine. Locomotor sensitization was induced by 4 daily cocaine injections and the phosphorylation status of GluR1 glutamate receptors was assayed in brain samples. Minocycline failed to affect cocaine sensitization in 5-LOX-deficient mice. In these mice, neither cocaine nor minocycline 4-day treatment altered GluR1 phosphorylation. In WT mice in which minocycline inhibited development of cocaine sensitization, a 4-day cocaine treatment increased GluR1 phosphorylation at both Ser831 and Ser845 sites in the frontal cortex but not the striatum; further, this effect was prevented by minocycline. Under basal conditions and in response to a single cocaine injection the levels of GluR1, GluR2, and GluR3 AMPA receptor subunits did not differ between WT and 5-LOX-deficient mice, but the response of GluR1 phosphorylation to a single cocaine injection was greater under the 5-LOX deficiency. Hence, in WT mice GluR1 phosphorylation increased only in the frontal cortex and only at the Ser831 site. In 5-LOX-deficient mice, acute cocaine injection increased both Ser831 and Ser845 phosphorylation both in the frontal cortex and in the striatum. We suggest that in studying minocycline's action on cocaine's effects and/or addiction in humans, it would be important to consider the characterization of the subjects' 5-LOX system. This article is part of a Special Issue entitled 'Trends in neuropharmacology: in memory of Erminio Costa'.
[Show abstract][Hide abstract] ABSTRACT: Interference of antibacterial agents with the immune system, and its possible clinical implications, has long been a focus
of attention worldwide. Toxic effects with immunological implications (neutropenia, allergy, etc.) exerted an influence on
the therapeutic choice early in the antimicrobial era, but attention has gradually shifted to beneficial “immunomodulatory”
properties. Many papers in this field have been published and it has been periodically reviewed [1, 2]. Interest in “immunostimulation”
peaked in the 1970s. Only recently have the potential benefits of downregulating immunomodulators entered the limelight, with
the understanding that immune hyperactivation (in sepsis and inflammatory/autoimmune diseases, for example) can also have
disastrous consequences. Incidental observations that some non-infectious diseases, including inflammatory disorders, may
be improved by antibacterials have bolstered interest in the immunomodulatory activity of this class of drugs. An improved
knowledge of the immune system and its regulation, as well as technological advances, has facilitated such investigations.
With a growing number of supportive experimental and clinical studies, the relevance of the immunomodulatory actions of some
antibiotics for their therapeutic efficacy in various diseases is now generally admitted.
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