Tetracyclines and Neuromuscular Disorders

Daniele      Orsucci; Michelangelo      Mancuso; Massimiliano      Filosto; Gabriele      Siciliano

doi:10.2174/157015912800604498

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.

Keywords: Doxycycline, mitochondria, minocycline, neurodegeneration, PARP-1, progressive external ophthalmoplegia, ROS, tetracycline