Levels of reduced and oxidized coenzymeQ-10 and 8-hydroxy-2′-deoxyguanosine in the cerebrospinal fluid of patients with living Parkinson's disease demonstrate that mitochondrial oxidative damage and/or oxidative DNA damage contributes to the neurodegenerative process

Isobe, Chiaki; Abe, Takashi; Terayama, Yasuo

doi:10.1016/j.neulet.2009.11.065

Cited by 105 publications

(73 citation statements)

References 27 publications

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“…Markers that would reflect key changes in these interrelated processes have therefore been of great interest. Altered redox status in PD has been demonstrated in studies of two potent antioxidants, coenzyme Q10 in blood 35,36 and CSF 37 and glutathione in plasma samples. 38 Oxidative damage to DNA has been demonstrated in PD by detection of elevated levels of 8-hydroxy-2-deoxyguanosine, …”

Section: Markers Of Oxidative Stress and Mitochondrial Dysfunctionmentioning

confidence: 99%

Blood and cerebrospinal fluid markers in Parkinson's disease: current biomarker findings

Henchcliffe

2014

CBF

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Abstract:Parkinson's disease (PD) is a common, progressive, and disabling neurodegenerative movement disorder. Signs and symptoms begin insidiously and overlap with other neurodegenerative conditions, making diagnosis challenging in early disease. Moreover, there are as yet no established biomarkers that will objectively measure disease progression, and this hampers efforts to obtain neuroprotective therapies. At present, diagnosis, measurement of progression, and response to therapeutic intervention rely almost exclusively upon clinical observation. There remains, therefore, a critical need for validated biomarkers. Recent advances in understanding the underlying pathophysiology of PD have aided in identifying strong candidate markers to assist in diagnosis and evaluate progression. Pathways that are disrupted in PD include protein misfolding, mitochondrial dysfunction and increased oxidative stress, dysregulated inflammatory processes, and altered gene expression. For example, α-synuclein is a key contributor to PD pathology, in which misfolded and damaged α-synuclein accumulates in neurons; this is now a leading candidate as a PD biomarker in cerebrospinal fluid. There is also recent evidence that markers of Alzheimer's disease may be "repurposed" to provide information on PD diagnosis, prognosis, and nonmotor symptoms, including cognitive dysfunction. At the same time, increasingly sophisticated bioinformatics technology allows an unbiased approach to biomarker identification, for example, using proteomic, transcriptomic, and metabolomic analysis. Such generally accessible blood or cerebrospinal fluid tests, if successful, will likely lead to significant improvements in PD diagnosis, management, and research.

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Section: Markers Of Oxidative Stress and Mitochondrial Dysfunctionmentioning

confidence: 99%

Blood and cerebrospinal fluid markers in Parkinson's disease: current biomarker findings

Henchcliffe

2014

CBF

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“…The levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of oxidative nucleic acid damage, are increased in cerebrospinal fluid of PD patients (45) and MPTP mice (4,5). To determine the effects of WIN55,212-2 and HU210 on MPTP-induced oxidative damage in nucleic acids, we immunostained for 8-OHdG.…”

Section: Win55212-2 and Hu210 Attenuate Mptp-induced Oxidative Damagesmentioning

confidence: 99%

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

Chung

Bok

Huh

et al. 2011

The Journal of Immunology

109

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This study examined whether the cannabinoid receptor type 1 (CB1) receptor contributes to the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. MPTP induced significant loss of nigrostriatal DA neurons and microglial activation in the substantia nigra (SN), visualized with tyrosine hydroxylase or macrophage Ag complex-1 immunohistochemistry. Real-time PCR, ELISA, Western blotting, and immunohistochemistry disclosed upregulation of proinflammatory cytokines, activation of microglial NADPH oxidase, and subsequent reactive oxygen species production and oxidative damage of DNA and proteins in MPTP-treated SN, resulting in degeneration of DA neurons. Conversely, treatment with nonselective cannabinoid receptor agonists (WIN55,212-2 and HU210) led to increased survival of DA neurons in the SN, their fibers and dopamine levels in the striatum, and improved motor function. This neuroprotection by cannabinoids was accompanied by suppression of NADPH oxidase reactive oxygen species production and reduced expression of proinflammatory cytokines from activated microglia. Interestingly, cannabinoids protected DA neurons against 1-methyl-4-phenyl-pyridinium neurotoxicity in cocultures of mesencephalic neurons and microglia, but not in neuron-enriched mesencephalic cultures devoid of microglia. The observed neuroprotection and inhibition of microglial activation were reversed upon treatment with CB1 receptor selective antagonists AM251 and/or SR14,716A, confirming the involvement of the CB1 receptor. The present in vivo and in vitro findings clearly indicate that the CB1 receptor possesses anti-inflammatory properties and inhibits microglia-mediated oxidative stress. Our results collectively suggest that the cannabinoid system is beneficial for the treatment of Parkinson’s disease and other disorders associated with neuroinflammation and microglia-derived oxidative damage.

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“…Correlated with PD severity [14] [9] α-Synuclein↓ [7,22] 71% sensitivity and 53% specificity patients with PD vs. controls, DLB, and MSA [22] Phosphorylated α-synuclein↑ [21,23] No correlation between the α-synuclein level and PD severity [7,19,22,24] Antibody towards monomeric α-synuclein↑ [25] Tau Total tau↓ [26] Distinguish Patients with low UA levels in serum may be more prone to developing PD, and an inverse relationship between UA and severity of PD was robust for men but weak for women [11]. Another study in the Chinese population reported similar results, which suggests that the serum UA level could be a useful biomarker of PD diagnosis and disease progression [12].…”

Section: ↑[14]mentioning

confidence: 99%

“…Increased levels of oxidative stress have been reported in CSF, plasma and urine of patients with various neurodegenerative disorders. A study has found that the concentration of 8-OHdG in CSF of PD patients was greater than that in CSF of controls (p < 0.0001) and was positively correlated with the duration of disease [r(s) = 0.87, p < 0.001] [14]. Bolner and colleagues studied the ratio between 8-OHdG and 2-dG (which is related to the efficacy of the DNA repairing mechanisms) in plasma as a marker of oxidative stress in PD.…”

Section: ↑[14]mentioning

confidence: 99%

Recent advances in biomarkers for Parkinson’s disease focusing on biochemicals, omics and neuroimaging

Ren¹,

Sun²,

Zhao³

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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Abstract:Parkinson's disease (PD) is one of the most common neurodegenerative disorders, involving progressive loss of the nigro-striatal dopaminergic neurons. Cardinal symptoms including tremors, muscle rigidity, drooping posture, drooping, walking difficulty, and autonomic symptoms appear when a significant number of nigrostriatal dopaminergic neurons have already been destroyed. Hence, reliable biomarkers are needed for early and accurate diagnosis to measure disease progression and response to therapy. We review the current status of protein and small molecule biomarkers involved in oxidative stress, protein aggregation and inflammation etc. which are present in cerebrospinal fluid, human blood, urine or saliva. In recent years, advances in genomics, proteomics, metabolomics, and functional brain imaging techniques have led to new insights into the pathoetiology of PD. Further studies in the novel discovery of PD biomarkers will provide avenues to treat PD patients more effectively with few or no side effects.

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Levels of reduced and oxidized coenzymeQ-10 and 8-hydroxy-2′-deoxyguanosine in the cerebrospinal fluid of patients with living Parkinson's disease demonstrate that mitochondrial oxidative damage and/or oxidative DNA damage contributes to the neurodegenerative process

Cited by 105 publications

References 27 publications

Blood and cerebrospinal fluid markers in Parkinson's disease: current biomarker findings

Blood and cerebrospinal fluid markers in Parkinson's disease: current biomarker findings

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

Recent advances in biomarkers for Parkinson’s disease focusing on biochemicals, omics and neuroimaging

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Levels of reduced and oxidized coenzymeQ-10 and 8-hydroxy-2′-deoxyguanosine in the cerebrospinal fluid of patients with living Parkinson's disease demonstrate that mitochondrial oxidative damage and/or oxidative DNA damage contributes to the neurodegenerative process

Cited by 105 publications

References 27 publications

Blood and cerebrospinal fluid markers in Parkinson&#39;s disease: current biomarker findings

Blood and cerebrospinal fluid markers in Parkinson&#39;s disease: current biomarker findings

Cannabinoid Receptor Type 1 Protects Nigrostriatal Dopaminergic Neurons against MPTP Neurotoxicity by Inhibiting Microglial Activation

Recent advances in biomarkers for Parkinson’s disease focusing on biochemicals, omics and neuroimaging

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Blood and cerebrospinal fluid markers in Parkinson's disease: current biomarker findings

Blood and cerebrospinal fluid markers in Parkinson's disease: current biomarker findings