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Review
. 2015 Jun;24(2):103-16.
doi: 10.5607/en.2015.24.2.103. Epub 2015 Jun 8.

Mitochondrial Dysfunction in Parkinson's Disease

Hyo Eun Moon  1 , Sun Ha Paek  1
Affiliations
Review

Mitochondrial Dysfunction in Parkinson's Disease

Hyo Eun Moon et al. Exp Neurobiol. 2015 Jun.

Abstract

Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta (SNc) with motor and nonmotor symptoms. Defective mitochondrial function and increased oxidative stress (OS) have been demonstrated as having an important role in PD pathogenesis, although the underlying mechanism is not clear. The etiopathogenesis of sporadic PD is complex with variable contributions of environmental factors and genetic susceptibility. Both these factors influence various mitochondrial aspects, including their life cycle, bioenergetic capacity, quality control, dynamic changes of morphology and connectivity (fusion, fission), subcellular distribution (transport), and the regulation of cell death pathways. Mitochondrial dysfunction has mainly been reported in various non-dopaminergic cells and tissue samples from human patients as well as transgenic mouse and fruit fly models of PD. Thus, the mitochondria represent a highly promising target for the development of PD biomarkers. However, the limited amount of dopaminergic neurons prevented investigation of their detailed study. For the first time, we established human telomerase reverse transcriptase (hTERT)-immortalized wild type, idiopathic and Parkin deficient mesenchymal stromal cells (MSCs) isolated from the adipose tissues of PD patients, which could be used as a good cellular model to evaluate mitochondrial dysfunction for the better understanding of PD pathology and for the development of early diagnostic markers and effective therapy targets of PD. In this review, we examine evidence for the roles of mitochondrial dysfunction and increased OS in the neuronal loss that leads to PD and discuss how this knowledge further improve the treatment for patients with PD.

Keywords: PD genes; mitochondrial dysfunction; oxidative stress; pathophysiology.

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Figures

Fig. 1
Fig. 1. Mitochondria dysfunction and dopaminergic cell death in PD pathogenesis. Multiple factors, including genetics, aging and environmental toxins, or combinations, have been implicated in the aetiology of PD. Abnormal metabolic function, abnormal morphology, and impaired fission-fusion balance have all been observed in mitochondria in at least some forms of PD. Increased OS can lead to impaired function of the UPS, thereby further affecting cell survival. All these may directly or indirectly affect the mitochondrial function of protein degradation systems, including UPS and ALP, and thereby, cause the death of dopamine neurons.
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