Potential of PINK1 and PARKIN Proteins as Biomarkers for Active Multiple Sclerosis: A Japanese Cohort Study.

Background: Mitochondrial dysfunction has been suggested to play an important role in all stages of multiple sclerosis (MS). Objective: To determine the expression of two mitophagy-related proteins, PTEN-induced kinase 1 (PINK1) and PARKIN, in a cohort of Japanese patients with different neuroinflammatory disorders. Methods: Protein concentrations were measured using commercial ELISA in paired cerebrospinal fluid (CSF) and serum samples from patients with multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein antibody disorders (MOGAD), and from age- and sex-matched controls. Results: CSF and serum concentrations of PINK1 were higher in patients with MS than in patients with NMOSD (p = 0.004 and p < 0.001, respectively), MOGAD (p = 0.008 and p = 0.011, respectively), and controls (p = 0.021 and p = 0.002, respectively). CSF and concentrations of PARKIN were elevated in patients with MS in comparison with those in controls (p = 0.016 and p = 0.05, respectively). Conclusions: Our study highlighted the importance of mitophagy in MS and suggested the potential application of PINK1 and PARKIN as biomarkers to predict disease activity.

The relationship between ANT1 and NFL with autophagy and mitophagy markers in patients with multiple sclerosis.

Multiple sclerosis (MS) is the most common inflammatory neurodegenerative disease. Neurofilament light chain (NFL) is a novel adverting biomarker of axonal damage that suggested as a useful assistant in the monitoring of MS patients. It has been shown that the auto/mitophagy associated with MS pathogenesis. In this study, we aimed to study correlation between ATG5 and Parkin, as markers of autophagy and mitophagy respectively, with NFL and ANT1 in serum and cerebrospinal fluid (CSF) in MS subjects. ATG5, Parkin, NFL, and ANT1 levels were measured in a cross-sectional study of 40 MS patients compared with gender, age and BMI matching healthy volunteers. Based on our results, levels of ATG5, Parkin, and NFL significantly were elevated in both serum and CSF of MS patients comparing control individuals (p < 0.0001) but ANT1 levels significantly was decreased in both serum and CSF of MS patients comparing control individuals (p < 0.0001). The correlation indices between NFL, ANTI1, ATG5 and Parkin in both case and control groups showed a direct and moderate the correlation between ANTI1 and ATG5 in the CSF level of the control group (r = 0.554, P = 0.011). Our data support the feasibility of quantifying of NFL as a sensitive and clinically meaningful serum/CSF biomarker to follow-up nerve tissue injury in MS condition.

Proteomic analysis of cerebrospinal fluid in Alzheimer's disease: wanted dead or alive.

Clinical diagnosis of Alzheimer's disease (AD) relying on symptomatic features has a low specificity, emphasizing the importance of the pragmatic use of neurochemical biomarkers. The most advanced and reliable markers are amyloid-ß (Aß42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) with relatively high levels of sensitivity, specificity, and diagnostic accuracy. Recent advances within the field of proteomics offer the potential to search for novel biomarkers in CSF by using modern methods, such as microarrays. The purpose of this study was to identify pathognostic proteins in CSF obtained from patients whose clinical AD diagnosis was confirmed by the "core" biomarkers. CSF samples were obtained from 25 AD patients and 25 control individuals. The levels of Aß42, t-tau, and p-tau were measured by ELISA. In the microarray experiments, ultrasensitive slides representing of 653 antigens were used. Apolipoprotein E genotyping was also determined. A decrease of seven CSF proteins in AD were found, four of them (POLG, MGMT, parkin, and ApoD) have a protective function against neuronal death, while the remaining three proteins (PAR-4, granzyme B, Cdk5) trigger multiple pathways facilitating neuronal cell death. Since these proteins from CSF samples could not be identified by western blot, their decreased levels in AD patients were not verified. Our results provide new information of pathognostic importance of POLG and granzyme B in AD. Although the function of MGMT, parkin, ApoD, PAR-4, and Cdk5 was previously known in AD, the findings presented here provide novel evidence of the significance of CSF analysis in the mapping of the AD pathomechanism.