The diagnosis of PD might be in difficulty, especially in the early stages. Therefore, the identification of novel biomarkers is imperative for the diagnosis and monitoring disease progression in PD. DJ-1 and α-synuclein, are two proteins that are critically involved in the pathogenesis of PD, and they have been examined as disease biomarkers in studies. However, no study exists regarding DJ-1 in plasma neural-derived exosomes. In the present study, the levels of DJ-1 and α-synuclein in plasma neural-derived exosomes were studied together in order to investigate novel biomarkers for PD. DJ-1 and α-synuclein in plasma and plasma neural-derived exosomes of the patients with PD and controls were quantified by ELISAs. The data revealed that the levels of DJ-1 and α-synuclein in plasma neural-derived exosomes and the ratio of plasma neural-derived exosomal DJ-1 to total DJ-1 were significantly higher in patients with PD, compared with controls, while levels of the two proteins in plasma exhibited no difference between the patients with PD and controls. However, no relationship was identified between biomarkers and disease progression. In addition, significant positive correlations between DJ-1 and α-synuclein in plasma neural-derived exosomes were found in the patients with PD and in healthy individuals. We hypothesize that DJ-1 in plasma neural-derived exosomes may be used as a potential biomarker as α-synuclein in PD and they might participate in the mechanism of PD together.

BackgroundParkinson’s disease is a high incidence neurodegenerative disease in elderly people, and oxidative stress plays an important role in the pathogenesis. Oxygen metabolism in the brain is high, which lacks an antioxidative protection mechanism. Recently, it has been found that polyphenols play an important role in antioxidation. (−)-epigallocatechin-3-gallate (EGCG) is an important component of tea polyphenols and its biological effects, such as strong antioxidation, scavenging of free radicals and anti-apoptosis, can pass through the blood brain barrier. The SIRT1/PGC-1α signaling pathway has not been reported in PC12 cells. Therefore, research of the protective mechanism of EGCG in PC12 cells damaged by -methyl-4-phenyl-pyridine (MMP+) may provide a new insight into protect against and treatment of Parkinson’s disease.MethodsMPP+-treated highly differentiated PC12 cells were used as the in vitro cell model. An MTT assay was used to investigate cell viability after EGCG treatment, a dichlorofluorescin diacetate assay was used to measure reactive oxygen species (ROS) production, western blot analysis was used to observe PGC-1α and SIRT1 protein expression, and real-time PCR to observe PGC-1α, SOD1 and GPX1 mRNA expression.ResultsPC12 cell viability was significantly reduced after MPP+ treatment by 11.46% compared with that of the control (P < 0.05). However, cell viability was unchanged by 10 μmol/L EGCG treatment. In co-treatments with EGCG and MPP+, cell viability was significantly increased by 12.92% (P < 0.05) and MPP+-induced ROS production was markedly decreased. PGC-1α mRNA expression was obviously upregulated by 21.51% (P < 0.05), and SOD1 and GPX1 mRNA expression was slightly increased by 12.94% and 15.63% (P > 0.05), respectively, by treatment with EGCG and then MPP+ for 12 h. The mRNA expression of PGC-1α, SOD1 and GPX1 was increased by 25.17%, 40% and 146% (all P < 0.05), respectively, by treatment with EGCG and then MPP+ for 24 h. Such effects were not observed with MPP+ treatment alone.ConclusionThe SIRT1/PGC-1α pathway is one of the mechanisms of EGCG suppression of MPP+-induced injury of PC12 cells.

Background New therapies are urgently needed for Alzheimer’s disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. Methods We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician’s Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. Results A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was − 2.15 points (95% confidence interval, − 3.07 to − 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. Conclusions GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. Trial registration ClinicalTrials.gov, NCT02293915. Registered on November 19, 2014

When patients transition from PD-NCI to PD-MCI, there appears to be an increase in functional connectivity in the PCC, suggesting an expansion of the cortical network. Another new network (a compensatory prefrontal cortical-cerebellar loop) later develops during the transition from PD-MCI to PDD.