Evidence for Oxidative Pathways in the Pathogenesis of PD: Are Antioxidants Candidate Drugs to Ameliorate Disease Progression?

Parkinson's disease (PD) is a progressive neurodegenerative disorder that arises due to a complex and variable interplay between elements including age, genetic, and environmental risk factors that manifest as the loss of dopaminergic neurons. Contemporary treatments for PD do not prevent or reverse the extent of neurodegeneration that is characteristic of this disorder and accordingly, there is a strong need to develop new approaches which address the underlying disease process and provide benefit to patients with this debilitating disorder. Mitochondrial dysfunction, oxidative damage, and inflammation have been implicated as pathophysiological mechanisms underlying the selective loss of dopaminergic neurons seen in PD.

The Cyclic Nitroxide TEMPOL Ameliorates Oxidative Stress but Not Inflammation in a Cell Model of Parkinson's Disease.

The cyclic nitroxide TEMPOL exerts anti-oxidative and anti-inflammatory effects, and thus may provide therapeutic benefit in Parkinson's disease (PD), in which mitochondrial dysfunction, oxidative damage and inflammation have been implicated as pathophysiological mechanisms underlying the selective loss of dopaminergic neurons. Markers of oxidative stress and inflammation were investigated in a cell model of differentiated human neuroblastoma (SH-SY5Y) cells treated with the neurotoxin, 6-hydroxydopamine (6-OHDA). Treatment with TEMPOL ameliorated 6-OHDA-mediated cytotoxicity and attenuated biomarkers of oxidative stress including: mitochondrial superoxide anion free radical production, lipid peroxidation, induction of heme oxygenase 1 (HO-1) protein expression and NFκB activation.

Serum IgA1 shows increased levels of 2,6-linked sialic acid in breast cancer.

The lectin agglutinin (HPA) recognizes altered glycosylation in solid cancers and the identification of HPA binding partners in tumour tissue and serum is an important aim. Among the many HPA binding proteins, IgA1 has been reported to be the most abundant in liver metastases. In this study, the glycosylation of IgA1 was evaluated using serum samples from patients with breast cancer (BCa) and the utility of IgA1 glycosylation as a biomarker was assessed.

A targeted glycoproteomic approach identifies cadherin-5 as a novel biomarker of metastatic breast cancer.

Aberrant glycosylation has long been recognised as a hallmark of cancer, and is increasingly being exploited in biomarker discovery studies. Helix pomatia agglutinin (HPA) is known to bind aberrant glycans associated with metastatic breast cancer, and was used here to isolate glycoproteins from pooled breast cancer serum samples of (i) patients with recurrent breast cancer and (ii) patients with no sign of recurrence 5years after diagnosis of their primary tumour. Pregnancy zone protein, the polymeric immunoglobulin receptor and cadherin-5 emerged as potential markers of metastasis following proteomic identification of HPA binding glycoproteins.