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Mitochondrial Therapeutic Approaches in Parkinson’s Disease

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Mitochondrial Mechanisms of Degeneration and Repair in Parkinson's Disease

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Abstract

Mitochondria play a pivotal role in cellular metabolism since they regulate key aspects of cellular metabolism such as ATP production, intracellular calcium homeostasis, and endogenous reactive oxygen species production and decide cellular fate by regulating programmed cell death. Neurons are postmitotic cells that rely almost entirely on mitochondrial metabolism for ATP production, which renders these cells especially vulnerable to mitochondrial dysfunction. A great body of evidence links mitochondrial dysfunction to Parkinson’s disease (PD) etiopathogenesis, where mitochondrial abnormalities have been described in the brain and peripheral tissues. The identification of mutations that affect mitochondria in familial PD cases has provided a great inroad for the study of molecular mechanisms and placed mitochondria dysfunction as an upstream event in PD pathology. Previously we have proposed a mitochondrial cascade hypothesis for PD pathology, which allows inferring that mitochondria may be the bridge between sporadic and familial Parkinson’s disease. Here we review the latest advances on mitochondrial-targeted therapeutic approaches proposed for PD and discuss their potential as disease-modifying strategies.

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Abbreviations

6-OHDA:

6-Hydroxydopamine

ASYN:

alpha-Synuclein

CoQ10:

Coenzyme Q10

Cybrid:

Cytoplasmic hybrid

DA:

Dopamine

ETC:

Electron transport chain

HDAC6:

Histone deacetylase 6

LBs:

Lewy bodies

MitoQ:

Mitoquinone

MPP+ :

1-Methyl-4-phenylpyridinium

MPTP:

1-Methyl-4-phenyl-1,2,3,4-tetrahydropyridine

mtDNA:

Mitochondrial DNA

PARL:

Presenilin-associated rhomboid-like

PD:

Parkinson’s disease

PGC1α:

Peroxisome proliferator-activated receptor-γ coactivator 1α

PINK1:

PTEN-induced kinase 1

PPAR-γ:

Peroxisome proliferator-activated receptor gamma

ROS:

Reactive oxygen species

SNpc:

Substantia nigra pars compacta

SOD:

Superoxide dismutase

TPP:

Triphenyl phosphonium

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Acknowledgments

Work in our laboratory is supported by the Portuguese Foundation for Science and Technology (FCT-MCTES, Portugal) (PEst-C/SAU/LA0001/2013) and NEUROMED—SOE4/P1/E831. Silva DF and AR Esteves are supported by Postdoctoral Fellowship from FCT-MCTES, Portugal.

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Authors and Affiliations

  1. CNC—Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal

    Ana Raquel Esteves, Diana F. Silva, Maria G-Fernandes, Rui Gomes & Sandra Morais Cardoso

  2. Institute of Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Sandra Morais Cardoso

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  1. Ana Raquel Esteves
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  2. Diana F. Silva
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  3. Maria G-Fernandes
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  4. Rui Gomes
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  5. Sandra Morais Cardoso
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Correspondence to Sandra Morais Cardoso .

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  1. College of Health Sciences, Midwestern University, Glendale, Arizona, USA

    Lori M. Buhlman

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Esteves, A.R., Silva, D.F., G-Fernandes, M., Gomes, R., Cardoso, S.M. (2016). Mitochondrial Therapeutic Approaches in Parkinson’s Disease. In: Buhlman, L. (eds) Mitochondrial Mechanisms of Degeneration and Repair in Parkinson's Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-42139-1_9

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