Oxidative Stress in Parkinson's Disease: A Systematic Review and Meta-Analysis

Abstract

Oxidative stress has been suggested to play a key role in Parkinson's disease, but inconsistent results were found in clinical studies. This study sought to quantitatively summarize the blood and cerebrospinal fluid (CSF) oxidative stress marker data in PD patients. We performed a systematic search of PubMed and Web of Science, and studies were included if they provided data on peripheral blood and CSF oxidative stress marker concentrations in PD patients and healthy control (HC) subjects. Data were extracted by three independent investigators from 80 included studies encompassing 7,212 PD patients and 6,037 HC subjects. Of the 22 oxidative stress markers analyzed, random effects meta-analysis showed that blood concentrations of 8-OhdG, MDA, nitrite, and ferritin were increased in patients with PD compared with HC subjects. In contrast, we showed that blood levels of catalase, uric acid, glutathione, and total-cholesterol were significantly down-regulated in patients with PD when compared with controls. There were no significant differences between PD patients and HC subjects for blood, Mn, Cu, Zn, Fe, SOD, albumin, glutathione peroxidase, vitamin E, ceruloplasmin, triglycerides, lactoferrin, transferrin, LDL-cholesterol, and HDL-cholesterol. Due to the limited number of CSF studies with small sample size, this meta-analysis only showed non-significant association between CSF 8-OhdG and PD. The findings of our meta-analysis demonstrated higher blood concentrations of 8-OhdG, MDA, nitrite and ferritin, and lower blood concentrations of catalase, uric acid, glutathione and total-cholesterol in PD patients, strengthening the clinical evidence that PD is accompanied by increased oxidative stress.

Protein Deimination Signatures in Plasma and Plasma-EVs and Protein Deimination in the Brain Vasculature in a Rat Model of Pre-Motor Parkinson’s Disease

“…The interplay between oxidative stress and microRNAs has been shown in a number of neurodegenerative diseases including AD, PD, HD, and ALS [148]. Oxidative stress has indeed been suggested to play key roles in PD, although some parameters from clinical studies have been inconsistent [149]. Therefore, the identification in the current study of miR210 being significantly elevated in the pre-motor PD model indicates a hitherto unrecognized contribution by EV-mediated transport of this microRNA in early stages of PD.…”

Protection from the Pathogenesis of Neurodegenerative Disorders, including Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, Huntington’s Disease, and Parkinson’s Diseases, through the Mitigation of Reactive Oxygen Species

“…During their lifespan, dopamine neurons are constantly exposed to RNS and ROS from metabolic processes localized to the cytosol [152][153][154]. Being a comparatively unstable molecule, dopamine itself can produce ROS by undergoing auto-oxidation within the nigrostriatal tract system, indicating that oxidation may progress with aging [155,156]. In summary, accumulation of alpha-synuclein protein, impaired respiratory chain and somatic mitochondrial DNA mutations, iron accumulation, enhanced dopamine metabolism, increase in malondialdehyde and hydroperoxides in the substantia nigra, hydroxyl radical accumulation, and poor antioxidant status generates oxidative stress, particularly ROS in PD.…”

Adrenergic Receptors as Pharmacological Targets for Neuroinflammation and Neurodegeneration in Parkinson’s Disease

“…These genetic and nongenetic risk factors have the potential to initiate neurodegeneration and subsequent chronic inflammation in the brain which eventually contributes to the pathophysiology of PD [9]. In addition, several cellular and molecular pathways such as oxidative stress [10], proteosomal dysfunction [11], excitotoxicity [12], and mitochondrial dysfunction [13] have also been identified which contributes to neuronal death.…”