SOCIAS Sergio Benjamin
Tetracycline repurposing in neurodegeneration: focus on Parkinson’s disease
BORTOLANZA, MARIZA; NASCIMENTO, GLAUCE C.; SOCIAS, SERGIO B.; PLOPER, DIEGO; CHEHÍN, ROSANA N.; RAISMAN-VOZARI, RITA; DEL-BEL, ELAINE
JOURNAL OF NEURAL TRANSMISSION. GENERAL SECTION.
Año: 2018 p. 1 - 12
The prevalence of Parkinson?s disease, which affects millions of people worldwide, is increasing due to the aging population.In addition to the classic motor symptoms caused by the death of dopaminergic neurons, Parkinson?s disease encompassesa wide range of nonmotor symptoms. Although novel disease-modifying medications that slow or stop Parkinson?s diseaseprogression are being developed, drug repurposing, which is the use of existing drugs that have passed numerous toxicityand clinical safety tests for new indications, can be used to identify treatment compounds. This strategy has revealed thattetracyclines are promising candidates for the treatment of Parkinson?s disease. Tetracyclines, which are neuroprotective,inhibit proinflammatory molecule production, matrix metalloproteinase activity, mitochondrial dysfunction, protein misfolding/aggregation, and microglial activation. Two commonly used semisynthetic second-generation tetracycline derivatives,minocycline and doxycycline, exhibit effective neuroprotective activity in experimental models of neurodegenerative/neuropsychiatric diseases and no substantial toxicity. Moreover, novel synthetic tetracyclines with different biologicalproperties due to chemical tuning are now available. In this review, we discuss the multiple effects and clinical propertiesof tetracyclines and their potential use in Parkinson?s disease treatment. In addition, we examine the hypothesis that theanti-inflammatory activities of tetracyclines regulate inflammasome signaling. Based on their excellent safety profiles inhumans from their use for over 50 years as antibiotics, we propose the repurposing of tetracyclines, a multitarget antibiotic,to treat Parkinson?s disease.