Parkinson's disease (PD), one of the most common human neurodegenerative diseases, is characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain. PD is a complex disorder with multiple genetic and environmental factors influencing disease risk. To identify susceptible genes for sporadic PD, we performed case-control association studies of 268 single nucleotide polymorphisms (SNPs) in 121 candidate genes. In two independent case-control populations, we found that a SNP in alpha-synuclein (SNCA), rs7684318, showed the strongest association with PD (P=5.0 x 10(-10)). Linkage disequilibrium (LD) analysis using 29 SNPs in a region around rs7684318 revealed that the entire SNCA gene lies within a single LD block (D'>0.9) spanning approximately 120 kb. A tight LD group (r2>0.85) of six SNPs, including rs7684318, associated most strongly with PD (P=2.0 x 10(-9)-1.7 x 10(-11)). Haplotype association analysis did not show lower P-values than any single SNP within this group. SNCA is a major component of Lewy bodies, the pathological hallmark of PD. Aggregation of SNCA is thought to play a crucial role in PD. SNCA expression levels tended to be positively correlated with the number of the associated allele in autopsied frontal cortices. These findings establish SNCA as a definite susceptibility gene for sporadic PD.
Recently, we confirmed the presence of enhanced neural reconstruction in Parkinson's disease and in an animal model of Parkinson's disease based on increased polysialic acid-like immunoreactivity. Changes in neurogenesis often appear parallel to changes in angiogenesis. Moreover, both these processes share similar modulating factors, like vascular endothelial growth factor (VEGF) and its receptors VEGFR-1 (Flt-1) and VEGFR-2 (Flk-1). Using immunohistochemistry, we identified in this study upregulation of VEGF in the substantia nigra but not in the striatum of patients with Parkinson's disease by enzyme-linked immunosorbent assay. Such overexpression may participate in vascular remodeling and neurogenesis in the substantia nigra of Parkinson's disease.
Oxidative stress including DNA oxidation is implicated in Parkinson's disease (PD). We postulated that DNA repair enzymes such as 8-oxoguanosine DNA glycosylase (OGG1) are involved in the PD process. We performed immunohistochemical and biochemical studies on brains of patients with PD and those of patients with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) as disease controls, and control subjects. We found higher expression levels of mitochondrial isoforms of OGG1 enzymes in the substantia nigra (SN) in cases of PD. Furthermore, Western blot analysis revealed high OGG1 levels in the SN of the patients with PD. Our results indicate the importance of oxidative stress within the susceptible lesions in the pathogenesis of PD.
Considering that very few studies have assessed numerous clinical symptoms in the same report, these data provide a useful reference for the clinical course of PD.
There have been reports from several countries that hepatitis E virus (HEV) infection is frequently associated with Guillain-Barré syndrome (GBS). This study aimed to determine the frequency of HEV infection associated with GBS in Japanese patients, and to clarify the clinical characteristics of these patients. Sera obtained from 63 patients with GBS or Miller Fisher syndrome (MFS) and 60 control subjects were examined for both HEV-IgM and HEV-IgG. Of the 63 patients, three were positive for both HEV-IgM and elevated hepatic enzymes: Two had GBS, and one had MFS. No control subjects were positive for HEV-IgM. Our study demonstrated that 4.8 % of patients with GBS or MFS from our institution had associated acute HEV infection. There were no clinical differences between GBS with HEV infection and other GBS cases. To our knowledge, this is the first survey in Japan of HEV-associated GBS or MFS.
Background: Gastrointestinal symptoms are one of the most common non-motor features of Parkinson’s disease (PD). Recently, a report from Taiwan revealed that irritable bowel syndrome (IBS) may be associated with an increased risk of developing PD; however, the prevalence of IBS in PD patients has not been fully evaluated. Rome III criteria are widely assessed with a questionnaire to determine functional gastrointestinal disorders.Objective: We assessed the prevalence of constipation and IBS in PD patients in our cohort using Rome III criteria.Methods: Between October 2014 and April 2015, 118 patients with PD were treated at Fukuoka University Hospital and were enrolled in this study. Rome III criteria were used to diagnose constipation and IBS.Results: Constipation and IBS were detected in 32 (27.1%) and 20 patients (17.0%), respectively. The most common symptom related to constipation was straining during defecation (77.1%). Among constipation symptoms, patients’ self-awareness of constipation was mostly related to straining during defecation (odds ratio 5.27, 95% confidence interval 1.475–18.811). The number of constipation symptoms was correlated with the severity of the Hoehn-Yahr Stage (p < 0.05) and total levodopa equivalent dose (p < 0.05).Conclusions: This is the first report to investigate the prevalence of IBS in PD patients with Rome III criteria. We found a higher prevalence of IBS compared with the general population. The prevalence of constipation based on Rome III criteria was much lower than that reported in previous studies. Further studies are warranted to evaluate gastrointestinal symptoms in PD patients using comparable questionnaires.
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