Doxycycline, a semi-synthetic second-generation tetracycline, may be reproposed to treat synucleinopathies. This discovery is made by researchers from CCT-Tucumán and Instituto de Química Biológica Dr Bernabé Bloj (CONICET-UNT) in Argentina and Sorbonne Universités in France. The study, “Repurposing doxycycline for synucleinopathies: remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured specie,” appears in Scientific Reports. Synucleinopathies, also known as α-Synucleinopathies, refer to neurodegenerative disorders that involve the abnormal accumulation of the protein α-synuclein. It encompasses Parkinson’s disease, multiple system atrophy, and some other disorders. Protein aggregation, neuroinflammation, oxidative stress, and many other factors can damage neurons in the brain. (Cusabio offers α-synuclein and other proteins like Recombinant FADS1.) For many years, scientists have been searching for ways to combat these diseases. Unfortunately, there is no cure for them to date, as many experimental agents have failed to provide an effective neuro-protection in vivo or have proved ineffective in clinical trails. An attracted strategy to tackle this problem is to repurpose existing drugs against new targets. Previous studies in animal models of Parkinson’s disease have shown that the antibiotic doxycycline has neuroprotective activity: it reduces the loss of dopamine-producing neurons and nerve terminals in the brain. The possible mechanism is related to its ability to inhibit neuroinflammation. Other studies have found that doxycycline has an additional target. It suppressed fibril formation of amyloidogenic proteins such as Aβ peptide, PrP peptide and β-microglobulin. In this work, the team conducted a series of experiments to explore the precise mechanism by which doxycycline affects α-synuclein aggregation. Results showed that the presence of doxycycline induces a remodeling of α-synuclein oligomers into off-pathway non-toxic, non-seeding species. This further explains why doxycycline exhibits neuroprotective effect on models in vivo. Doxycycline is a widely used antibiotic in humans, which is typically used to treat infections caused by bacteria and protozoa. It is safe and has good penetration of the blood–brain barrier. Findings of this study suggest that potential the protective side effects for doxycycline in the pathogenesis cycle of synucleinopathies could be exploited repurposing an old safe drug, the researchers concluded.
