Mitochondria: A Therapeutic Target for Parkinson's Disease?
Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The exact causes of neuronal damage are unknown, but mounting evidence indicates that mitochondrial-mediated pathways contribute to the underlying mechanisms of dopaminergic neuronal cell death both in PD patients and in PD animal models. Mitochondria are organized in a highly dynamic tubular network that is continuously reshaped by opposing processes of fusion and fission. Defects in either fusion or fission, leading to mitochondrial fragmentation, limit mitochondrial motility, decrease energy production and increase oxidative stress, thereby promoting cell dysfunction and death. Thus, the regulation of mitochondrial dynamics processes, such as fusion, fission and mitophagy, represents important mechanisms controlling neuronal cell fate. In this review, we summarize some of the recent evidence supporting that impairment of mitochondrial dynamics, mitophagy and mitochondrial import occurs in cellular and animal PD models and disruption of these processes is a contributing mechanism to cell death in dopaminergic neurons. We also summarize mitochondria-targeting therapeutics in models of PD, proposing that modulation of mitochondrial impairment might be beneficial for drug development toward treatment of PD.
Department of Neurological Surgery, Case Western Reserve University, Cleveland, OH 44106, USA. yxl710@case.edu.
Yu
Y
Luo
Department of Neurological Surgery, Case Western Reserve University, Cleveland, OH 44106, USA. Alan.Hoffer@uhhospitals.org.
Alan
A
Hoffer
Department of Neurological Surgery, Case Western Reserve University, Cleveland, OH 44106, USA. bhoffer@intra.nida.nih.gov.
Barry
B
Hoffer
Department of Physiology, Case Western Reserve University, Cleveland, OH 44106, USA. xxq38@case.edu.
Xin
X
Qi
D000818:Animals; D001343:Autophagy / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D063154:Mitochondrial Dynamics / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D063306:Mitophagy / Q000235:genetics; D058990:Molecular Targeted Therapy; D009154:Mutation; D010084:Oxidation-Reduction / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D015398:Signal Transduction / Q000187:drug effects; D014118:Toxins, Biological / Q000633:toxicity
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D014118:Toxins, Biological
Parkinson’s disease; mitochondrial dynamics; mitochondrial dysfunction