Introduction: Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, with several proposed pathogenic mechanisms. Given the established role of mitochondrial dysfunction in PD, this study seeks to investigate the enrichment of rare genetic variants tied to mitochondrial metabolism in cases of early-onset and familial PD. Methods: We performed a retrospective analysis on 248 early-onset and familial PD patients and 1622 control individuals. We assessed both pathway-level and gene-level burden of germline rare variants detected using exome sequencing in 467 nuclear genes related to mitochondrial metabolism. Results: Gene-set mutation burden analysis indicated an increased burden in genes associated with mtDNA maintenance. In addition, gene-level analysis identified a possible association between PD and rare variant burden in 14 mitochondrial metabolism-related genes under dominant or recessive inheritance models. Conclusions: Our findings support a potential contribution of rare germline variants affecting mitochondrial metabolism to the susceptibility in early-onset and familial PD.

Stroke is characterized by a sudden onset of neurological deficit attributed to a focal brain injury. The main treatments for patients with an acute ischemic stroke are intravenous thrombolysis and mechanical thrombectomy. Recanalization therapies have significantly improved patient outcomes; however, their effectiveness depends on a range of pathophysiological factors. This prospective observational study included 60 patients with acute ischemic stroke. The control group consisted of 20 healthy blood donors. Patients were divided into three groups based on whether they received intravenous thrombolysis, mechanical thrombectomy, or combination therapy. We investigated differences between recanalization therapies in patients with ischemic stroke with respect to peripheral blood concentrations of the proinflammatory cytokine interleukin (IL)-18 and endothelial glycocalyx degradation products: syndecan-1, heparan sulphate, and hyaluronic acid, measured by enzyme-linked immunosorbent assay. The blood samples were collected before, 24, and 48 h after recanalization therapy. The concentration of IL-18, syndecan-1, and heparan sulphate increased statistically significantly in patients treated with mechanical thrombectomy. The concentration of hyaluronic acid increased statistically significantly in patients treated with intravenous thrombolysis. The findings primarily reflect between-group differences. Our findings indicate that IL-18 has a significant role in the early inflammatory response. IL-18 and EG degradation products represent potential biomarkers for identifying high-risk patients. Their measurement could help improve the treatment, recovery, and outcomes in patients with acute ischemic stroke. The aforementioned observations underscore their potential value as biomarkers for future research.

The aim of the present study was to investigate the impact of CCR5 Δ32 and CTLA-4 polymorphisms on the response to IFN-β treatment in our cohort of MS patients from Croatia and Slovenia. Genomic DNA was obtained from 295 MS patients (230 female; 65 male) classified as responders (n = 173) and non-responders (n = 122) based on clinical criteria for treatment efficacy. Genotyping was performed via PCR/PCR-RFLP. No significant differences in the genotype/allele frequencies of CCR5Δ32 and CTLA-4 +49 A/G were detected between male responders and non-responders. A significantly higher prevalence (p = 0.039) of the CTLA-4 +49 AA genotype was found in female responders (42.1%) compared to non-responders (28.9%). Using multiple forward regression analysis, the CTLA-4 +49 AA genotype significantly predicted a positive response to IFN-β therapy in females (p = 0.011) and contributed to 4.5% of response variability. Furthermore, the combined presence of the CCR5Δ32 wtwt/CTLA-4 +49 AA genotype significantly predicted a positive response to treatment in females (p = 0.025). The age at disease onset, pretreatment relapse rate, and baseline EDSS score were not reliable predictors of treatment response in MS patients. Our results indicate that the presence of the CCR5Δ32 polymorphism was not associated with the response to IFN-β treatment, whereas the CTLA-4 +49 polymorphism showed a positive correlation with an optimal response in female patients.