Nonmercaptalbumin as an oxidative stress marker in Parkinson’s and PARK2 disease

Abstract

Objective To investigate the oxidized albumin ratio, which is the redox ratio of human nonmercaptalbumin (HNA) to serum albumin (%HNA), as a biomarker in idiopathic Parkinson’s disease (iPD) and related neurodegenerative disorders. Methods This prospective study enrolled 216 iPD patients, 15 patients with autosomal recessive familial PD due to parkin mutations (PARK2), 30 multiple system atrophy (MSA) patients, 32 progressive nuclear palsy (PSP) patients, and 143 healthy controls. HNA was analyzed using modified high‐performance liquid chromatography and was evaluated alongside other parameters. Results iPD and PARK2 patients had a higher %HNA than controls (iPD vs. controls: odds ratio (OR) 1.325, P < 0.001; PARK2 vs. controls: OR 1.712, P < 0.001). Even iPD patients at an early Hoehn & Yahr stage (I and II) showed a higher %HNA than controls. iPD patients had a higher %HNA than MSA and PSP patients (iPD vs. MSA: OR 1.249, P < 0.001, iPD vs. PSP: OR 1.288, P < 0.05). When discriminating iPD patients from controls, %HNA corrected by age achieved an AUC of 0.750; when discriminating iPD patients from MSA and PSP patients, an AUC of 0.747 was achieved. Furthermore, uric acid, an antioxidant compound, was decreased in iPD patients, similar to the change in %HNA. Interpretation %HNA was significantly increased in iPD and PARK2 patients compared with controls, regardless of disease course and severity. Oxidative stress might be increased from the early stages of iPD and PARK2 and play an important role in their pathomechanisms.

Serum Albumin Redox States: More Than Oxidative Stress Biomarker

“…Similarly, Rossi et al reported increases in cysteinylation and homocysteinylation of plasma proteins with aging in healthy subjects aged 20-93 [84]. Increases in HNA ratios with aging have been further confirmed in recent studies on patients and healthy controls [32,77]. The rationale for these observations has been attributed to oxidative stress accelerated by aging.…”

“…These observations were further substantiated by a cohort study on patients with head and neck squamous cell carcinomas, reporting that patients with higher oxidized ALB levels had higher plasma NET levels as well as higher incidences pulmonary cancer metastasis. Another recent study by Ueno et al showed that oxidized serum ALB increased in idiopathic and genetic Parkinson’s diseases [ 77 ]. These authors attributed this to accelerated aging-induced oxidative stress in these patients.…”

The Universal Soldier: Enzymatic and Non-Enzymatic Antioxidant Functions of Serum Albumin

“…It is known that in chronic liver and kidney diseases, as well as in diabetes mellitus, the percentage of cysteinylated albumin (Cys34-S-S-Cys) is markedly increased [ 116 ]. In recent years, it has been shown that oxidised albumin can be a biomarker of the severity of such diseases as hyperparathyroidism [ 152 ], acute ischemic stroke [ 153 ], Parkinson’s disease [ 154 ], Alzheimer’s disease [ 155 ], Duchenne muscular dystrophy [ 156 ], etc.…”

Advances of Mechanisms-Related Metabolomics in Parkinson’s Disease

“… Okuzumi et al (2019) analyzed serum metabolomics from Parkin patients and age-matched controls, and revealed higher levels of oxidized lipids and fatty acid metabolites and lower levels of antioxidant markers in PARK2 patients, suggesting the relationship between the serum/plasma metabolomics and gene dysfunction. Additionally, as a way of ensuring mitochondrial quality control, the mutation effects the elimination of dysfunctional mitochondria that was associated with an increase of mitochondrial stress, manifesting a systemic oxidative stress markers for the pathomechanisms of Parkin -mutation patients ( Ueno et al, 2020 ).…”