Open Close
Reference
Citation
Di Cristo, F., Finicelli, M., Digilio, F.A., Paladino, S., Valentino, A., Scialò, F., D'Apolito, M., Saturnino, C., Galderisi, U., Giordano, A., Melone, M.A.B., Peluso, G. (2019). Meldonium improves Huntington's disease mitochondrial dysfunction by restoring peroxisome proliferator-activated receptor γ coactivator 1α expression.  J. Cell. Physiol. 234(6): 9233--9246.
FlyBase ID
FBrf0241639
Publication Type
Research paper
Abstract

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.

PubMed ID
PubMed Central ID
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Cell. Physiol.
    Title
    Journal of Cellular Physiology
    Publication Year
    1966-
    ISBN/ISSN
    0021-9541
    Data From Reference
    Alleles (2)
    Genes (3)
    Human Disease Models (1)
    Transgenic Constructs (2)