Neurodegenerative diseases are a group of disorders characterized by progressive loss of certain populations of neurons, which eventually lead to dysfunction. These diseases include Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Immune pathway dysregulation is one of the common features of neurodegeneration. Recently, there is growing interest in the specific role of T helper Th 17 cells and Interleukin-17A (IL-17A), the most important cytokine of Th 17 cells, in the pathogenesis of the central nervous system (CNS) of neurodegenerative diseases. In the present study, we summarized current knowledge about the function of Th17/IL-17A, the physiology of Th17/IL-17A in diseases, and the contribution of Th17/IL-17A in AD, PD, and ALS. We also update the findings on IL-17A-targeting drugs as potentially immunomodulatory therapeutic agents for neurodegenerative diseases. Although the specific mechanism of Th17/IL-17A in this group of diseases is still controversial, uncovering the molecular pathways of Th17/IL-17A in neurodegeneration allows the identification of suitable targets to modulate these cellular processes. Therapeutics targeting IL-17A might represent potentially novel anti-neurodegeneration drugs.

Objective: To investigate the serum levels of inflammatory cytokines and the correlations with Parkinson’s disease (PD) clinical symptoms.Methods: Serum levels of the cytokines, including IL-6, IL-8, and TNF-α, were measured in 273 PD patients and 91 healthy controls (HCs). The clinical manifestations of PD were assessed with nine different scales to evaluate the cognitive function, non-motor symptoms, motor symptoms, and disease severity. The differences in these inflammatory indicators were examined between PD patients and HCs, and the correlations of these inflammatory indicators with clinical variables were analyzed in PD patients.Results: Serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in PD patients were higher than those in HCs, but serum interleukin-8 (IL-8) level was not significantly different from that in HCs. In PD patients, serum IL-6 level was positively correlated with age of onset, the Hamilton Depression Scale (HAMD), and the Non-Motor Symptom Scale (NMSS), UPDRS part I, part II, and part III, but it was inversely correlated with the Frontal Assessment Battery (FAB) and the Montreal Cognitive Assessment (MoCA) scores. Serum TNF-α level was positively correlated with age of onset and H&Y stage in PD patients (p = .037), but negatively correlated with FAB scores in PD patients (p = .010). However, no associations were found between all the clinical variables and the serum IL-8 level. The forward binary logistic regression model revealed that serum IL-6 level was associated with MoCA (p = .023) and UPDRS I scores (p = .023), but no associations was found with the remaining factors. The ROC curve of TNF-α for the diagnosis of PD showed the area under the curve (AUC) was .719 (p < .05, 95% CI: .655–.784), and the critical value of TNF-α was 5.380 pg/ml, with a diagnostic sensitivity of 76.0% and a specificity of 59.3%.Conclusion: Our results suggest increased serum levels of IL-6 and TNF-α in PD, we further found that IL-6 level was associated with non-motor symptoms and cognitive dysfunction, and IL-6 may play a role in the pathophysiology of non-motor symptoms in PD. At the same time, we also propose that TNF-α has a good diagnostic value for PD despite its irrelevance to clinical symptoms.

Background: Ubiquitinated-protein aggregates are implicated in cerebral ischemia/reperfusion injury. The very presence of these ubiquitinated-protein aggregates is abnormal and seems to be disease-related. However, it is not clear what leads to aggregate formation and whether the aggregations represent a reaction to aggregate-mediated neurodegeneration. Methods: To study the nitrosative stress-induced protein aggregation in cerebral ischemia/reperfusion injury, we used primary astrocyte cultures as a cell model, and systematically examined their iNOS expression and consequent NO generation following oxygen glucose deprivation and reperfusion. The expression of protein disulfide isomerase (PDI) and copper-zinc superoxide dismutase (SOD1) were also examined, and the biochemical interaction between PDI and SOD1 was determined by immunoprecipitation. In addition, the levels of S-nitrosylated PDI in cultured astrocytes after oxygen glucose deprivation and reperfusion treatment were measured using the biotin-switch assay. The formation of ubiquitinated-protein aggregates was detected by immunoblot and immunofluorescence staining. Results: Our data showed that the up-regulation of iNOS expression after oxygen glucose deprivation and reperfusion treatment led to excessive NO generation. Up-regulation of PDI and SOD1 was also identified in cultured astrocytes following oxygen glucose deprivation and reperfusion, and these two proteins were found to bind to each other. Furthermore, the increased nitrosative stress due to ischemia/reperfusion injury was highly associated with NO-induced S-nitrosylation of PDI, and this S-nitrosylation of PDI was correlated with the formation of ubiquitinated-protein aggregates; the levels of S-nitrosylated PDI increased in parallel with the formation of aggregates. When NO generation was pharmacologically inhibited by iNOS specific inhibitor 1400W, S-nitrosylation of PDI was significantly blocked. In addition, the formation of ubiquitinated-protein aggregates in cultured astrocytes following oxygen glucose deprivation and reperfusion was also suppressed by 1400W. Interestingly, these aggregates were colocalized with SOD1, which was found to co-immunoprecipitate with PDI. Conclusions: NO-mediated S-nitrosylation of PDI may be involved in the formation of the SOD1-linked ubiquitinated-protein aggregates in cerebral ischemia/reperfusion injury.

The aim of the study was to assess a panel of promising biomarkers for their ability to improve diagnosis of sporadic amyotrophic lateral sclerosis (ALS). Forty patients with sporadic ALS and 40 controls with other neurological diseases were evaluated. Levels of phosphorylated neurofilament heavy chain (pNfH), S100-β, cystatin C, and chitotriosidase (CHIT) in cerebrospinal fluid were assayed using two-site solid-phase sandwich ELISA. Patients with sporadic ALS showed higher levels of pNfH and CHIT than controls, but lower levels of cystatin C. Multivariate logistic regression that adjusted for patient age and sex identified significant associations between sporadic ALS and levels of pNfH, CHIT and cystatin C. Levels of pNfH correlated positively with rate of progression and decline based on the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised. Based on receiver operating curve analysis, a pNfH cut-off of 437 ng/L discriminated patients from controls with a sensitivity of 97.3 % and specificity of 83.8 %. A CHIT cut-off of 1593.779 ng/L discriminated patients from controls with a sensitivity of 83.8 % and specificity of 81.1 %. Combining the two biomarkers gave a sensitivity of 83.8 % and specificity of 91.9 %. Levels of pNfH in cerebrospinal fluid may be a reliable biomarker for diagnosing ALS, and combining this biomarker with levels of CHIT may improve diagnostic accuracy.

Background: Studies have investigated the lipid profile in amyotrophic lateral sclerosis (ALS), including the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and higher low-density lipoprotein (LDL), and the associations with mortality of ALS, but the results were inconsistent. Therefore, we conducted this meta-analysis to systematically answer this unsolved question. Methods: We searched all the related studies that probed into the association between serum lipid levels and ALS based on PubMed, EMBASE, and Cochrane library from January 1990 to July 2020. The quality of the included studies was evaluated by using the Newcastle–Ottawa Scale (NOS). All the statistical analyses of this meta-analysis were performed using the Stata version 12.0 software. Results: Fourteen studies with a total of 3,291 ALS patients and 3,367 controls were included. Among them, 10 studies compared the lipid profile between ALS patients and controls. The results indicated that compared with controls, ALS patients from both Europe and Asia had lower levels of TG and HDL, but the levels of TC and LDL were higher in ALS patients from Europe. However, after systemic analyses, the altered TC level was significant only in Asian ALS patients; the differences of other lipids were not significant. Concerning the effect of lipid profile on mortality of ALS, analyses of four cohort studies showed that the levels of all lipids were not associated with overall mortality in ALS. Conclusion: The results of the present study showed that Asian ALS patients had lower TC levels than controls, and the levels of all lipids were not associated with mortality of ALS.

This pilot study was intended to evaluate the effects of active game play on cognition, quality of life, and depression for older people with dementia.Thirty-eight older people with dementia were r...