Higher serum levels of pro-hepcidin in patients with Parkinson's disease treated with deep brain stimulation.

Hepcidin is an essential hormone responsible for the systemic metabolism of iron and simultaneously belongs to the family of the protein mediators of the acute inflammatory response, primarily induced in response to interleukin 6. It can therefore be regarded as a link between the oxidative stress processes, where iron plays an important role, and the processes of neuroinflammation - both considered to be responsible for the neurodegeneration in Parkinson's disease. We assessed the serum level of pro-hepcidin in patients with Parkinson's disease treated only pharmacologically and those treated additionally with deep brain stimulation (DBS) as compared to the control group. Thirty-seven patients with Parkinson's disease (18 females, 19 males, mean age: 57 years) were treated only pharmacologically with optimal, individualized therapy for each patient, whereas 15 (7 females, 8 males, mean age: 54 years) were treated additionally with DBS. The control group consisted of 31 healthy volunteers (15 females, 16 males, mean age: 58 years). In the subgroup of patients with Parkinson's disease treated with DBS the serum concentration of pro-hepcidin was significantly higher and the result was statistically significantly higher than in the control group (p = 0.0003) and in patients with Parkinson's disease treated only pharmacologically (p = 0.025). The results suggested the possible immunomodulatory effect of prolonged high-frequency stimulation and the implantation of the electrodes into the brain tissue of the host, most likely in the form of the increasaed production of inflammatory mediators, associated with the activation of the astroglia and microglia. The rational justification for the purpose of our study was the evidences and hypothesis from studies on the potential immunomodulatory and neuroprotective effect of DBS in patients with Parkinson's disease, the systemic influence of the DBS procedure on the improvement of motor function, reduction of dopaminergic drugs, improvement of the quality of life of patients, and animal studies, which have proven the presence of regional neuroinflammation around implanted electrodes.

Incidence of mutations in the PARK2, PINK1, PARK7 genes in Polish early-onset Parkinson disease patients.

BACKGROUND AND PURPOSE: Parkinson disease (PD) is a complex disease, comprising genetic and environmental factors. Despite the vast majority of sporadic cases, three genes, i.e. PARK2, PINK1 and PARK7 (DJ-1), have been identified as responsible for the autosomal recessive form of early-onset Parkinson disease (EO-PD). Identified changes of these genes are homozygous or compound heterozygous mutations. The frequency of PARK2, PINK1 and PARK7 mutations is still under debate, as is the significance and pathogenicity of the single heterozygous mutations/variants, which are also detected among PD patients. The aim of the study was to analyze the incidence of autosomal recessive genes PARK2, PINK1, PARK7 mutations in Polish EO-PD patients. MATERIAL AND METHODS: The analysis of the PARK2, PINK1 and PARK7 genes was performed in a group of 150 Polish EO-PD patients (age of onset < 45 years). Mutation analysis was based on sequencing and gene dosage abnormality identification. RESULTS: Mutations were identified only in the PARK2 and PINK1 genes with the frequency of 4.7% and 2.7% of subjects, respectively. In PARK2, point mutations and exons' rearrangements, and in PINK1 only missense mutations were detected. In both genes mutations were found as compound heterozygous/homozygous and single heterozygous. EO-PD patients' genotype-phenotype correlation revealed similarities of clinical features in mutation carriers and non-carriers. CONCLUSIONS: The frequency of the PARK2, PINK1, PARK7 mutations among Polish EO-PD patients seems to be low. The role of single heterozygous mutations remains a matter of debate and needs further investigations.

[Factors which can play important role in pathogenesis of Parkinson disease]. / Czynniki, które moga odgrywac istotna role w patogenezie choroby Parkinsona.

Degeneration of dopaminergic neurons that project from substantia nigra to striatum is the primary mechanism that causes Parkinson disease (PD). This death of dopaminergic cells disturbs control over impulses sent from the motor cortex and hence results in the presence of three cardinal motor signs: tremor, rigidity, bradykinesia. The cause of Parkinson disease is unknown. Current treatments relieve symptoms but do not halt the progression of the disease. It is not yet known what causes neurons to degenerate. Influences of aging, environmental toxins, genetic susceptibility have been pointed out by researchers, but the theory of oxidative stress seems to be the most convincing. It is supposed that SN neurons are exposed to oxidative reactions from dopamine metabolism (production) during which hydrogen peroxide and toxic semiquinones are formed. Additionally, in brains of PD patients there are decreased concentrations of defence mechanisms such as glutathion and compensatory ferritin that binds iron, maintaining it in its safe state (Fe2+ iron takes part in Fenton reaction that leads to free radicals production). However, we have to admit that Parkinson disease is probably multifactorial, and the combination of the above stated factors may cause the disease.