Inflammatory and Cell Death Pathways in Brain and Peripheral Blood in Parkinson’s Disease

Macchi, Beatrice; Paola, Rosanna Di; Marino-Merlo, Francesca; Felice, Maria Rosa; Cuzzocrea, Salvatore; Mastino, Antonio

doi:10.2174/1871527314666150225124928

Cited by 75 publications

(51 citation statements)

References 121 publications

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“…Several studies confirmed the fact of the ability of antioxidants to protect the cells from apoptosis [43,53]. Another mechanism of antiapoptotic properties of ML is through inhibition of inflammation [54].…”

Section: Discussionmentioning

confidence: 82%

Protective Effect of Montelukast against Cadmium Induced Pituitary Gland Toxicity

Ek¹,

Mf²,

Mg³

et al. 2017

IJCPT

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Adult male Sprague rats weighting (220 ± 30gm) were purchased from Faculty of Agriculture, Minia University Egypt. Experimen- AbstractCadmium (Cd) is a common environmental hazardous heavy metal. The standard treatment of heavy metal intoxication; chelators may have a minor role in Cd toxicity. Montelukast (ML) is an anti-inflammatory drug that is used mainly for managing asthmatic patients. Recent workers have tested ML for its antioxidant properties in various conditions and obtained encouraging results as regarding this effect. We investigated the protective and antioxidant effect of ML on pituitary gland, a highly sensitive organ to Cd toxicity. Four groups of rats were used and received distilled water, 10mg/kg ML, 3mg/kg Cd, and 10mg ML plus 3mg/kg Cd respectively. Antioxidant, histological, immunohistochemical and hormonal effects of Cd and ML were evaluated. The detrimental effect of Cd on pituitary gland was abolished by ML. The diminished hormonal effect of Cd was restored to normal levels. The increased MDA level and depleted oxidative enzymes on pituitary gland of rat exposed to Cd were restored by ML. lastly, histological and apoptotic effects of Cd were also, corrected significantly by ML. It is concluded that ML can protect against Cd-induced pituitary gland toxicity.

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Section: Discussionmentioning

confidence: 82%

Protective Effect of Montelukast against Cadmium Induced Pituitary Gland Toxicity

Ek¹,

Mf²,

Mg³

et al. 2017

IJCPT

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“…This neuron death, accompanied by the breakdown of the blood-brain barrier, causes the release of DNA into the plasma. Furthermore, since PD patients have increased systemic inflammation and peripheral cell death that are correlated with disease severity, increased cell death with the release of DNA into the plasma may occur (Lin et al, 2014b, 2015; Macchi et al, 2015; Yu et al, 2016). Either way, the levels of plasma nuclear DNA may rise.…”

Section: Discussionmentioning

confidence: 99%

Associations among Cognitive Functions, Plasma DNA, and White Matter Integrity in Patients with Early-Onset Parkinson's Disease

Chen

et al. 2017

Front. Neurosci.

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Early-onset Parkinson's disease (EOPD) patients are symptomatic at a relatively young age, and the impacts of the disease on both the patients and their caregivers are dramatic. Few studies have reported on the cognitive impairments seen in EOPD, and the results of these studies have been diverse. Furthermore, it is still unclear what microstructural white matter (WM) changes are present in EOPD patients. As such, we conducted this study to investigate the microstructural WM changes experienced by EOPD patients and their association with cognitive function and plasma DNA levels. We enrolled 24 EOPD patients and 33 sex- and age-matched healthy volunteers who underwent complete neuro-psychological testing (NPT) to evaluate their cognitive function and diffusion tensor imaging (DTI) scanning to determine their fiber integrity. The plasma DNA measurements included measurements of nuclear and mitochondrial DNA levels. Fractional anisotropy (FA) maps were compared using voxel-based statistics to determine differences between the two groups. The differences in DTI indices and NPT scores were correlated after adjusting for age, sex, and education. Our results demonstrate that patients with EOPD have elevated nuclear DNA levels and wide spectrums of impairments in NPT, especially in the executive function and visuospatial function domains. Exploratory group-wise comparisons of the DTI indices revealed that the patients with EOPD exhibited lower DTI parameters in several brain locations. These poorer DTI parameters were associated with worse cognitive performances and elevated plasma nuclear DNA levels, especially in the anterior thalamic radiation region. Our findings suggest that the thalamus and its adjacent anterior thalamic radiation may be important in the pathogenesis of EOPD, as they appear to become involved in the disease process at an early stage.

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“…Although the pathogenesis of PD has not been completely elucidated, inflammation has been identified both in the brain and peripheral blood of PD patients, and correlates with the development and progression of PD [23,24]. Activated microglia, T lymphocytes, and an increased expression of proinflammatory cytokines as well as growth factors have been found in the substantia nigra of PD patients in postmortem studies [25,26].…”

Section: Discussionmentioning

confidence: 99%

Serum Growth Differentiation Factor 15 in Parkinson Disease

Yao

Wang

Zhang³

et al. 2017

Neurodegener Dis

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Background: Growth differentiation factor 15 (GDF15) has been shown to be protective for dopaminergic neurons in animal and ex vivo experiments. However, little is known about its effect on the human body. Objective: This study investigated associations between serum GDF15 levels and clinical parameters in patients with Parkinson disease (PD). Methods: Idiopathic PD patients (n = 104) and age-matched controls (n = 88) were enrolled. Serum GDF15 levels were measured by human enzyme-linked immunosorbent assay. Univariate and multivariate analyses investigated correlations between GDF15 and clinical characteristics, including disease severity by the Unified PD Rating Scale (UPDRS)-III. The diagnostic value of GDF15 was evaluated by receiver-operating characteristic curve (ROC) analysis. Results: The serum GDF15 levels of the PD patients were significantly higher than those of the healthy controls. In PD patients, serum GDF15 levels in men were significantly higher than in women. GDF15 levels correlated with age, gender, disease duration, and UPDRS-III score. After adjusting for confounding factors, multiple linear regression analysis showed that the serum GDF15 level (β = 0.015, p = 0.001) was an independent risk factor for UPDRS-III score. In ROC analysis, GDF15 achieved an area under the curve of 0.86 for the identification of PD, with a sensitivity of 71.15% and a specificity of 87.50%. Conclusion: GDF15 may be a potential biomarker for the diagnosis and monitoring of motor severity in PD.

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Inflammatory and Cell Death Pathways in Brain and Peripheral Blood in Parkinson’s Disease

Cited by 75 publications

References 121 publications

Protective Effect of Montelukast against Cadmium Induced Pituitary Gland Toxicity

Protective Effect of Montelukast against Cadmium Induced Pituitary Gland Toxicity

Associations among Cognitive Functions, Plasma DNA, and White Matter Integrity in Patients with Early-Onset Parkinson's Disease

Serum Growth Differentiation Factor 15 in Parkinson Disease

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