No abstract

Although emerging evidence suggests that the pathogenesis of Parkinson’s disease (PD) is closely related to the aggregation of alpha-synuclein (α-syn) in the midbrain, the clearance of α-syn remains an unmet clinical need. Here, we develop a simple and efficient strategy for fabricating the α-syn nanoscavenger for PD via a reprecipitation self-assembly procedure. The curcumin analogue-based nanoscavenger (NanoCA) is engineered to be capable of a controlled-release property to stimulate nuclear translocation of the major autophagy regulator, transcription factor EB (TFEB), triggering both autophagy and calcium-dependent exosome secretion for the clearance of α-syn. Pretreatment of NanoCA protects cell lines and primary neurons from MPP+-induced neurotoxicity. More importantly, a rapid arousal intranasal delivery system (RA-IDDS) was designed and applied for the brain-targeted delivery of NanoCA, which affords robust neuroprotection against behavioral deficits and promotes clearance of monomer, oligomer, and aggregates of α-syn in the midbrain of an MPTP mouse model of PD. Our findings provide a clinically translatable therapeutic strategy aimed at neuroprotection and disease modification in PD.

Hypertension (HTN) is a leading cause of cardiovascular and cerebrovascular diseases. Lifestyle modification may be the preferential approach to prevent and control HTN. The purpose of this study was to evaluate the effects of a community intervention program, which focused on improving the HTN knowledge, diets and lifestyles in a rural Chinese area. The study was carried out in a rural area of the Hubei Province from May 2003 to April 2006. A total of 1632 participants were recruited. Of the participants, 826 from the town of Xiaoxita and 806 from the town of Fenxiang were assigned to the intervention group (group I) and to the control group (group C), respectively. Group I participants underwent an intervention that included HTN education and dietary and lifestyle guidance. Group C participants were not subjected to an intervention. The outcome measures included HTN knowledge, dietary and lifestyle behaviors, and prevalence, awareness, treatment and control rates of HTN. Along with the changes in HTN education (Po0.05), the participants in group I exhibited a significantly greater improvement in dietary habits and lifestyle behaviors, including reducing salty food intake (13.6%), fat intake (22.9%) and alcohol consumption (9.6%), after 3 years in comparison with those in group C (21.7, 31.9 and 18%, respectively). The prevalence of HTN was significantly lower in group I (22.5%) than in group C (36%) after the intervention strategies. The study showed that the implementation of a community intervention program involving HTN education and lifestyle modifications for rural residents is a powerful approach to reduce HTN prevalence and improve long-term health outcomes.

Ginsenoside Rb1 has been demonstrated to protect dopaminergic (DA) neurons from death in vitro. However, the neuroprotective effects and underlying mechanism of Rb1 in treating Parkinson's disease (PD) remain uncharacterized. In this study, we explored the effects of Rb1 on the movement disorder and the underlying mechanisms based on the glutamatergic transmission and excitotoxicity in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Here, for the first time, we report that Rb1 treatment ameliorates motor deficits, prevents DA neuron death, and suppresses α-synuclein expression and astrogliosis in the MPTP mouse model of PD. Rb1 attenuates glutamate excitotoxicity by upregulating glutamate transporter expression and function, and modulating the nigrostriatal and cortico-nigral glutamatergic transmission pathways. Our results demonstrate that Rb1 increases glutamate transporter expression via nuclear translocation of nuclear factor-kappa B, regulates glutamate receptor expression and promotes synaptic protein expression. These results indicate that Rb1 suppresses glutamate excitotoxicity and modulates synaptic transmission to improve the impairments in motor functions of the MPTP model of PD, suggesting that Rb1 may serve as a potential therapeutic agent for PD.