Title:Tetracyclines and Neuromuscular Disorders
Volume: 10
Issue: 2
Author(s): Daniele Orsucci, Michelangelo Mancuso, Massimiliano Filosto and Gabriele Siciliano
Affiliation:
Keywords:
Doxycycline, mitochondria, minocycline, neurodegeneration, PARP-1, progressive external ophthalmoplegia,
ROS, tetracycline
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.
