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Pharmacol Res. 2016 Nov;113(Pt A):563-573. doi: 10.1016/j.phrs.2016.09.043. Epub 2016 Sep 30.

Forty years later: Mitochondria as therapeutic targets in muscle diseases.

Author information

1
CNR Neuroscience Institute and Department of Biomedical Sciences, University of Padova, Padova, Italy.
2
CNR Neuroscience Institute and Department of Biomedical Sciences, University of Padova, Padova, Italy. Electronic address: bernardi@bio.unipd.it.

Abstract

The hypothesis that mitochondrial dysfunction can be a general mechanism for cell death in muscle diseases is 40 years old. The key elements of the proposed pathogenetic sequence (cytosolic Ca2+ overload followed by excess mitochondrial Ca2+ uptake, functional and then structural damage of mitochondria, energy shortage, worsened elevation of cytosolic Ca2+ levels, hypercontracture of muscle fibers, cell necrosis) have been confirmed in amazing detail by subsequent work in a variety of models. The explicit implication of the hypothesis was that it "may provide the basis for a more rational treatment for some conditions even before their primary causes are known" (Wrogemann and Pena, 1976, Lancet, 1, 672-674). This prediction is being fulfilled, and the potential of mitochondria as pharmacological targets in muscle diseases may soon become a reality, particularly through inhibition of the mitochondrial permeability transition pore and its regulator cyclophilin D.

KEYWORDS:

Calcium; Cyclophilins; Mitochondria; Muscle diseases; Permeability transition; Therapy

PMID:
27697642
DOI:
10.1016/j.phrs.2016.09.043
[Indexed for MEDLINE]

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