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J Neural Transm (Vienna). 2018 Oct;125(10):1403-1415. doi: 10.1007/s00702-018-1913-1. Epub 2018 Aug 14.

Tetracycline repurposing in neurodegeneration: focus on Parkinson's disease.

Author information

1
Department of Morphology, Physiology and Basic Pathology, Faculty of Odontology of Ribeirão Preto, University of São Paulo (USP), Av do Café s/n, São Paulo, Brazil.
2
Center of Interdisciplinary Research on Applied Neurosciences (NAPNA), USP, São Paulo, Brazil.
3
Instituto de Investigación en Medicina Molecular y Celular Aplicada (IMMCA) (CONICET/UNT/SIPROSA), Pasaje Dorrego, 1080-4000, Tucumán, Argentina.
4
Sorbonne Universite, UPMC Univ Paris 06, INSERM, CNRS, UM75, U1127, UMR 7225, Institut du Cerveau et de la Moelle Epinière, Paris, France. ritaraisman@gmail.com.
5
Department of Morphology, Physiology and Basic Pathology, Faculty of Odontology of Ribeirão Preto, University of São Paulo (USP), Av do Café s/n, São Paulo, Brazil. eadelbel@usp.br.
6
Center of Interdisciplinary Research on Applied Neurosciences (NAPNA), USP, São Paulo, Brazil. eadelbel@usp.br.

Abstract

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 encompasses a wide range of nonmotor symptoms. Although novel disease-modifying medications that slow or stop Parkinson's disease progression are being developed, drug repurposing, which is the use of existing drugs that have passed numerous toxicity and clinical safety tests for new indications, can be used to identify treatment compounds. This strategy has revealed that tetracyclines 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 biological properties due to chemical tuning are now available. In this review, we discuss the multiple effects and clinical properties of tetracyclines and their potential use in Parkinson's disease treatment. In addition, we examine the hypothesis that the anti-inflammatory activities of tetracyclines regulate inflammasome signaling. Based on their excellent safety profiles in humans from their use for over 50 years as antibiotics, we propose the repurposing of tetracyclines, a multitarget antibiotic, to treat Parkinson's disease.

KEYWORDS:

Antibiotic; Doxycycline; Drug repurposing; Neuroprotection; Parkinson’s disease; Tetracycline

PMID:
30109452
DOI:
10.1007/s00702-018-1913-1
[Indexed for MEDLINE]

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