Search Results (5)

Concussion diagnosis is difficult and may be improved with the addition of a blood-based biomarker that indicates concussion. The purpose of this research was to investigate the capability of serum amyloid beta precursor protein (APP), neurofilament light (NfL), and visinin-like protein-1 (VILIP-1) to distinguish athletes who were diagnosed with a concussion pitch-side. An observational cross-sectional study design was used to replicate sideline concussion diagnosis. Subjects included mutually exclusive pre-match (n = 9), post-match (n = 15), and SRC (n = 7) groups. Six paired pre-and post-match subjects were analyzed for APP. APP increased significantly from pre-match (mean = 57.98 pg·mL⁻¹, SD = 63.21 pg·mL⁻¹) to post-match (mean = 111.37 pg·mL⁻¹, SD = 106.89 pg·mL⁻¹, p = 0.048) in the paired subjects. NfL was lower in the SRC group (median = 8.71 pg·mL⁻¹, IQR = 6.09 pg·mL⁻¹) compared to the post-match group (median = 29.60 pg·mL⁻¹, IQR = 57.45 pg·mL⁻¹, p < 0.001). VILIP-1 was higher in the post-match group (median = 212.18 pg·mL⁻¹, IQR = 345.00 pg·mL⁻¹) compared to both the pre-match (median = 32.63 pg·mL⁻¹, IQR = 52.24 pg·mL⁻¹), p = 0.001) and SRC (median = 30.21 pg·mL⁻¹, IQR = 47.20 pg·mL⁻¹), p = 0.003) groups. APP, NfL, and VILIP-1 were all able to distinguish between pre-match and post-match groups (AUROC > 0.700) but not from the SRC group (AUROC < 0.660). Our results show that APP, NfL, and VILIP-1 were not helpful in differentiating concussed from non-concussed athletes pitch-side in this study. Full article

Synaptic loss and dysfunction are one of the earliest signs of neurodegeneration associated with cognitive decline in Alzheimer’s disease (AD) and other neurodegenerative diseases. This study aimed to assess the relationships between biological processes of the synaptic pathology underlying AD, molecular functions, and dynamics of the change concentrations of selected proteins reflecting synaptic and axonal pathology in dementia stages. Neurogranin (Ng), neuronal pentraxin receptor (NPTXR), and Visinin-like protein 1 (VILIP1) concentrations were measured in the cerebrospinal fluid (CSF) of MCI, AD, and non-demented controls (CTRL) using quantitative immunological methods. Gene ontology (GO) enrichment analysis was used for the functional analysis of tested proteins. The CSF Aβ42/Ng ratio was significantly different between all the compared groups. The CSF NPTXR/Ng ratio was significantly different between MCI compared to CTRL and AD compared to CTRL. The GO enrichment analysis revealed that two terms (the Biological Process (BP) and Cellular Component (CC) levels) are significantly enriched for NPTXR and Ng but not for VILIP1. Both Ng and NPTXR concentrations in CSF are promising synaptic dysfunction biomarkers for the early diagnosis of the disease. Moreover, both proteins are biochemically associated with classical biomarkers and VILIP-1. Mapping shared molecular and biological functions for the tested proteins by GO enrichment analysis may be beneficial in screening and setting new research targets. Full article

Neuronal calcium sensors (NCSs) are the family of EF-hand proteins mediating Ca²⁺-dependent signaling pathways in healthy neurons and neurodegenerative diseases. It was hypothesized that the calcium sensor activity of NCSs can be complemented by sensing fluctuation of intracellular zinc, which could further diversify their function. Here, using a set of biophysical techniques, we analyzed the Zn²⁺-binding properties of five proteins belonging to three different subgroups of the NCS family, namely, VILIP1 and neurocalcin-δ/NCLD (subgroup B), recoverin (subgroup C), as well as GCAP1 and GCAP2 (subgroup D). We demonstrate that each of these proteins is capable of coordinating Zn²⁺ with a different affinity, stoichiometry, and structural outcome. In the absence of calcium, recoverin and VILIP1 bind two zinc ions with submicromolar affinity, and the binding induces pronounced conformational changes and regulates the dimeric state of these proteins without significant destabilization of their structure. In the presence of calcium, recoverin binds zinc with slightly decreased affinity and moderate conformational outcome, whereas VILIP1 becomes insensitive to Zn²⁺. NCALD binds Zn²⁺ with micromolar affinity, but the binding induces dramatic destabilization and aggregation of the protein. In contrast, both GCAPs demonstrate low-affinity binding of zinc independent of calcium, remaining relatively stable even at submillimolar Zn²⁺ concentrations. Based on these data, and the results of structural bioinformatics analysis, NCSs can be divided into three categories: (1) physiological Ca²⁺/Zn²⁺ sensor proteins capable of binding exchangeable (signaling) zinc (recoverin and VILIP1), (2) pathological Ca²⁺/Zn²⁺ sensors responding only to aberrantly high free zinc concentrations by denaturation and aggregation (NCALD), and (3) Zn²⁺-resistant, Ca²⁺ sensor proteins (GCAP1, GCAP2). We suggest that NCS proteins may therefore govern the interconnection between Ca²⁺-dependent and Zn²⁺-dependent signaling pathways in healthy neurons and zinc cytotoxicity-related neurodegenerative diseases, such as Alzheimer’s disease and glaucoma. Full article

Postoperative recovery can be impaired by many conditions, some of which are difficult to diagnose clinically. These include type 2 neurological complications such as hypoactive subtype of postoperative delirium (PD) and early postoperative cognitive dysfunction (ePOCD). Hope for their timely detection may lie with novel biomarkers. Plasma concentrations of microRNA-1-3p, microRNA-21-5p, glial fibrillary acidic protein (GFAP), neuroserpin (NSP), phosphorylated axonal neurofilament subunit H (pNfH) and visinin-like protein 1 (VILIP-1) were investigated in 30 patients undergoing elective off-pump coronary artery bypass grafting. Blood samples were collected at the start and end of a surgery as well as 24 h postoperatively. Associations between the studied biomarkers’ perioperative expression and type 2 neurological complications were analyzed. PD was associated with postoperative expression of GFAP; ePOCD was associated with postoperative expression of microRNA-21-5p and GFAP as well as intraoperative expression of NSP. The predictive accuracy of these molecules was found acceptable, with all their areas under the curve (AUC) values above 0.7. Multivariable regression indicated that microRNA-21-5p, GFAP and NSP were the only significant predictors of ePOCD. Evaluation of a multi-marker model including these three molecules revealed its outstanding predictive accuracy for ePOCD (AUC = 0.95). The use of microRNA-21-5p, GFAP and NSP for monitoring postoperative recovery warrants further research considering their potential to predict PD and ePOCD. Full article

Neurogranin (Ng) and visinin-like protein 1 (VILIP-1) are promising candidates for Alzheimer’s Disease (AD) biomarkers closely related to synaptic and neuronal degeneration. Both proteins are involved in calcium-mediated pathways. The meta-analysis was performed in random effects based on the ratio of means (RoM) with calculated pooled effect size. The diagnostic utility of these proteins was examined in cerebrospinal fluid (CSF) of patients in different stages of AD compared to control (CTRL). Ng concentration was also checked in various groups with positive (+) and negative (-) amyloid beta (Aβ). Ng highest levels of RoM were observed in the AD (n = 1894) compared to CTRL (n = 2051) group (RoM: 1.62). Similarly, the VILIP-1 highest values of RoM were detected in the AD (n = 706) compared to CTRL (n = 862) group (RoM: 1.34). Concentrations of both proteins increased in more advanced stages of AD. However, Ng seems to be an earlier biomarker for the assessment of cognitive impairment. Ng appears to be related with amyloid beta, and the highest levels of Ng in CSF was observed in the group with pathological Aβ+ status. Our meta-analysis confirms that Ng and VILIP-1 can be useful CSF biomarkers in differential diagnosis and monitoring progression of cognitive decline. Although, an additional advantage of the protein concentration Ng is the possibility of using it to predict the risk of developing cognitive impairment in normal controls with pathological levels of Aβ1-42. Analyses in larger cohorts are needed, particularly concerning Aβ status. Full article