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Lookup NU author(s): Dr Filippo Scialo
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© 2018 Wiley Periodicals, Inc. Mitochondrial dysfunction seems to play a fundamental role in the pathogenesis of neurodegeneration in Huntington’s disease (HD). We assessed possible neuroprotective actions of meldonium, a small molecule affecting mitochondrial fuel metabolism, in in vitro and in vivo HD models. We found that meldonium was able to prevent cytotoxicity induced by serum deprivation, to reduce the accumulation of mutated huntingtin (mHtt) aggregates, and to upregulate the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in mHTT-expressing cells. The PGC-1α increase was accompanied by the increment of mitochondrial mass and by the rebalancing of mitochondrial dynamics with a promotion of the mitochondrial fusion. Meldonium-induced PGC-1α significantly alleviated motor dysfunction and prolonged the survival of a transgenic HD Drosophila model in which mHtt expression in the nervous system led to progressive motor performance deficits. Our study strongly suggests that PGC-1α, as a master coregulator of mitochondrial biogenesis, energy homeostasis, and antioxidant defense, is a potential therapeutic target in HD.
Author(s): Di Cristo F, Finicelli M, Digilio FA, Paladino S, Valentino A, Scialo F, D'Apolito M, Saturnino C, Galderisi U, Giordano A, Melone MAB, Peluso G
Publication type: Article
Publication status: Published
Journal: Journal of Cellular Physiology
Year: 2019
Volume: 234
Issue: 6
Pages: 9233-9246
Print publication date: 01/06/2019
Online publication date: 26/10/2018
Acceptance date: 19/09/2018
ISSN (print): 0021-9541
ISSN (electronic): 1097-4652
Publisher: Wiley-Liss Inc.
URL: https://doi.org/10.1002/jcp.27602
DOI: 10.1002/jcp.27602
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