Mitochondrial proteomics as a selective tool for unraveling Parkinson’s disease pathogenesis

Pienaar, Ilse S.; Dexter, David T.; Burkhard, Pierre

doi:10.1586/epr.10.8

Cited by 20 publications

(11 citation statements)

References 210 publications

(232 reference statements)

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“…PD is believed to stem from multifactorial origins, with exposure to pesticides, advancing age and an inherent genetic vulnerability for developing the disease comprising the most prominent risk factors for sustaining PD [49]. Mitochondrial dysfunction has been detected in multiple tissues taken from individuals diagnosed with sporadic PD.…”

Section: Parkinson's Disease: Pathogenesismentioning

confidence: 99%

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Synaptic Protein Alterations in Parkinson’s Disease

et al. 2011

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Alterations occur within distal neuronal compartments, including axons and synapses, during the course of neurodegenerative diseases such as Parkinson's disease (PD). These changes could hold important implications for the functioning of neural networks, especially since research studies have shown a loss of dendritic spines locating to medium spiny projection neurons and impaired axonal transport in PD-affected brains. However, despite ever-increasing awareness of the vulnerability of synapses and axons, inadequate understanding of the independent mechanisms regulating non-somatic neurodegeneration prevails. This has resulted in limited therapeutic strategies capable of targeting these distinct cellular compartments. Deregulated protein synthesis, folding and degrading proteins, and protein quality-control systems have repeatedly been linked with morphological and functional alterations of synapses in the PD-affected brains. Here, we review current understanding concerning the proteins involved in structural and functional changes that affect synaptic contact-points in PD. The collection of studies discussed emphasizes the need for developing therapeutics aimed at deregulated protein synthesis and degradation pathways operating at axonal and dendritic synapses for preserving "normal" circuitry and function, for as long as possible.

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Section: Parkinson's Disease: Pathogenesismentioning

confidence: 99%

“…However, the exact extent to which mitochondrial-related events function either independently or in synergy to contribute towards PD pathology remains to be determined [49].…”

Section: Parkinson's Disease: Pathogenesismentioning

confidence: 99%

Synaptic Protein Alterations in Parkinson’s Disease

et al. 2011

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“…The mitochondrial proteome has also been shown to be altered in ischemic hearts in comparison with both control and ischemic preconditioned hearts (Kim et al 2006a). Mitochondria are also involved in neurodegenerative diseases, such as multiple sclerosis (Broadwater et al 2011), Alzheimer's, and Parkinson's disease, where the latter is influenced by the regulation of oxidative stress and apoptosis elicited by mitochondria (Pienaar et al 2010;Gianazza et al 2011). Oxidative stress and ROS have been described in numerous studies to increase during aging when mitochondrial activity is also decreasing.…”

Section: Mitochondrial Perturbations In Various Diseasesmentioning

confidence: 99%

Mitochondrial proteomics—a tool for the study of metabolic disorders

Gregersen

Hansen

Palmfeldt

2012

J of Inher Metab Disea

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Mitochondria are important for a number of life and death processes, such as energy production, creation of reactive oxygen species, and elicitation of stress responses. These responses range from induction of protein quality control and antioxidant systems to mitochondria elimination and cell death. Mitochondrial dysfunctions are involved in pathologies associated with many diseases, for example metabolic disorders, diabetes, cancers, cardiovascular and neurodegenerative diseases as well as obesity and aging. Mitochondrial proteomics can be a powerful tool in the study of these diseases, especially since it can cover mitochondrial proteins from several metabolic pathways, such as the citric acid cycle, fatty acid oxidation, and respiratory chain, as well as protein networks involved in stress responses. The mitochondrial proteome can consist of more than 1,000 different proteins. However, it is difficult to define the precise number, since mitochondria are dynamic and difficult to purify, and because an unknown number of proteins possess dual or multiple localization, depending on cell type and physiological conditions. This review describes several quantitative studies of proteins from mitochondria isolated by centrifugation, separated by various methods (e.g., electrophoresis and nanoLC), and analyzed by advanced mass spectrometry. We illustrate the methods by showing that multiple pathways and networks are affected in cells from patients carrying gene variations affecting a mitochondrial protein. The study of cultured skin fibroblasts from patients with ethylmalonic aciduria associated with variations in the genes coding for short-chain acyl-CoA dehydrogenase (SCAD) or ETHE1 are two of the examples. The possibility of obtaining mitochondrial proteomics data from whole cell proteomics studies is also exemplified by the involvement of liver mitochondria in metabolic syndrome.

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“…Model experiments on laboratory animals demon strated that chronic systemic administration of another complex I inhibitor, pesticide rotenone, caused death of dopaminergic neurons in substantia nigra, proteasome system dysfunction, impairments in DJ 1 protein, inclusions of α sinuclein, and appear ance of behavioral symptoms (bradykinesia, muscle rigidity, postural impairments, decreased locomotion) typical for PD [62][63][64][65]. Other neurotoxins, paraquat, maneb, 6 hydroxydopamine (which also inhibits mitochondrial complex IV and monoamine oxidase) also inhibit complex I and induce PD symptoms both in humans and experimental animals [66][67][68][69].…”

Section: Parkinson's Disease and Impaired Activities Of Mitochondrialmentioning

confidence: 99%