Repositioning Doxycycline for Treating Synucleinopathies: Evidence from a Pre-Clinical Mouse Model

Abstract

Synucleinopathies, including Parkinson’s disease and Lewy Body dementia remain orphan of valuable therapies capable to interfere with the disease pathogenesis despite the large number of symptomatic approaches adopted in clinical practice to manage these diseases. Treatments simultaneously affecting α-synuclein (α-syn) oligomerization and neuroinflammation may counteract Parkinson’s disease and related disorders. Recent data demonstrated that Doxycycline an antibiotic of the tetracycline class, can inhibit α-syn aggregation and exert anti-inflammatory activity. We herein investigate, for the first time, the potential therapeutic properties of Doxy in a human α-syn A53T transgenic mouse model of synucleinopathies by the evaluation of behavioural, biochemical and histopathological parameters.

Note:
Funding Information: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of Interests: None.

Ethical Approval: All experimental procedures were conducted in conformity with institutional guidelines, that are in compliance with national (D.L. n.26, G.U. 4 March 2014) and international guidelines and laws (EEC Council Directive 86/609, OJ L 358, 1, 12 December 1987, Guide for the Care and Use of Laboratory Animals, U.S. National Research Council, 1996), and were reviewed and approved by the intramural ethical committee.

Keywords: Tetracyclines, α-synuclein, oligomers, inflammation, neuroprotection, Lewy bodies dementia