Exp Neurobiol.  2015 Jun;24(2):103-116. 10.5607/en.2015.24.2.103.

Mitochondrial Dysfunction in Parkinson's Disease

• Moon HE
• Paek SH

• KMID: 2165544
• DOI: http://doi.org/10.5607/en.2015.24.2.103

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.

Keyword

mitochondrial dysfunction; oxidative stress; PD genes; pathophysiology

MeSH Terms

Animals
Cell Death
Diptera
Dopaminergic Neurons
Energy Metabolism
Fruit
Genetic Predisposition to Disease
Humans
Life Cycle Stages
Mesenchymal Stromal Cells
Mice
Mice, Transgenic
Mitochondria
Neurons
Oxidative Stress
Parkinson Disease*
Pathology
Quality Control
Substantia Nigra
Telomerase
Biomarkers
Telomerase