Abstract
Tetracyclines are a class of antibiotics which could act as neuroprotective molecules in several neurological disorders, such as Huntington disease, Parkinson disease, stroke and multiple sclerosis. The main biological effects of tetracyclines are the inhibition of microglial activation, the attenuation of apoptosis and the suppression of reactive oxygen species production. The anti-apoptotic effect of tetracyclines involves the mitochondrion, and the major target for neuroprotective effects of tetracyclines lies within the complex network that links mitochondria, oxidative stress and apoptosis.Neuromuscular disorders are due to dysfunction of motor neurons, peripheral nerves, neuromuscular junction, or skeletal muscle itself. Animal studies have shown that minocycline could play neuroprotective effects in amyotrophic lateral sclerosis, but these positive findings have not been replicated in patients. Other neuromuscular disorders which tetracyclines may benefit are Guillain-Barré syndrome and other neuropathies, muscular dystrophies and mitochondrial disorders. However, well-designed double-blind controlled trials are still needed. Further studies are strongly needed to establish the most appropriate timing and dosage, as well as the indications for which tetracyclines could be effective and safe.Here, we review the neuroprotective effects of tetracyclines in animal models, the clinical studies in humans, and we focus on their potential application in patients with neuromuscular disorders.
Highlights
Tetracyclines are a group of broad-spectrum antibiotics including tetracycline, doxycycline, minocycline, and others
We review the neuroprotective effects of tetracyclines in animal models, the clinical studies in humans, and we focus on their potential application in patients with neuromuscular disorders
Studies reported that minocycline reduced mitochondrial Ca2+ uptake, stabilized mitochondrial membranes, inhibited mitochondrial release into the cytosol of cytochrome c and other apoptotic factors, such as AIF
Summary
Tetracyclines are a group of broad-spectrum antibiotics including tetracycline, doxycycline, minocycline, and others. The injury-induced activation of microglia and leukocytes and the subsequent activation of neuropeptides involved in nociception processes (prodynorphin and pronociceptin) may be potential targets for the attenuation of neuropathic pain by minocycline, as observed in a rat model of neuropathic pain [30] Despite these apparently pleiotropic effects of tetracyclines in animal models of GBS and other neuropathies, no clinical trials are available to date. In “Leber” cybrids, the mitochondrial membrane potential was significantly conserved and the active-caspase-3/procaspase-3 ratio was decreased by minocycline [38] It has been reported an improvement in ocular motility in a patient with ocular mitochondrial myopathy (progressive external ophthalmoplegia) following treatment with tetracycline [39]. Our results did not formally support any effect of tetracycline on eye motility, but some possible protective effects could not be completely ruled out. i.e., a further analysis suggested a possible difference between the tetracycline group and the placebo group, significant at least for oblique motility, when comparing the ratio
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