Exploiting the therapeutic potential of ready-to-use drugs: repurposing antibiotics against amyloid aggregation in neurodegenerative diseases

SOCIAS, SERGIO B.; GONZALEZ-LIZARRAGA, FLORENCIA; AVILA, CESAR L.; VERA, CECILIA; ACUÑA, LEONARDO; SEPULVEDA-DIAZ, JULIA E.; DEL-BEL, ELAINE; RAISMAN-VOZARI, RITA; CHEHIN, ROSANA N.

PROGRESS IN NEUROBIOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2017

0301-0082

Neurodegenerative diseases are chronic and progressive disorders that affect specific regions ofthe brain, causing gradual disability and suffering that results in a complete inability of patientsto perform daily functions. Amyloid aggregation of specific proteins is the most commonbiological event that is responsible for neuronal death and neurodegeneration in variousneurodegenerative diseases. Therapeutic agents capable of interfering with the abnormalaggregation are required, but traditional drug discovery has fallen short. The exploration of newuses for approved drugs provides a useful alternative to fill the gap between the increasingincidence of neurodegenerative diseases and the long-term assessment of classical drugdiscovery technologies. Drug re-profiling is currently the quickest possible transition from benchto bedside. In this way, experimental evidence shows that some antibiotic compounds exertneuroprotective action through anti-aggregating activity on disease-associated proteins. Thefinding that many antibiotics can cross the blood-brain barrier and have been used for severaldecades without serious toxic effects makes them excellent candidates for therapeutic switchingtowards neurological disorders. The present review is, to our knowledge, the first extensiveevaluation and analysis of the anti-amyloidogenic effect of different antibiotics on well-knowndisease-associated proteins. In addition, we propose a common structural signature derived fromthe antiaggregant antibiotic molecules that could be relevant to rational drug discovery