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Neural progenitor cells (NPCs) therapy, a promising therapeutic strategy for neurodegenerative diseases, has a huge challenge to ensure high survival rate and neuronal differentiation rate. Cerium oxide (CeO 2 ) nanoparticles exhibit multienzyme mimetic activities and have shown the capability of regulating reactive oxygen species (ROS), which is a pivotal mediator for intracellular redox homeostasis in NPCs, regulating biological processes including differentiation, proliferation, and apoptosis. In the present study, the role of facet-dependent CeO 2 -mediated redox homeostasis in regulating self-renewal and differentiation of NPCs is reported for the first time. The cube-, rod-, and octahedron-shaped CeO 2 nanozymes with different facets are prepared. Among the mentioned nanozymes, the cube enclosed by the (100) facet exhibits the highest CAT-like activity, causing it to provide superior protection to NPCs from oxidative stress induced by H 2 O 2 ; meanwhile, the octahedron enclosed by the (111) facet with the lowest CAT-like activity induces the most ROS production in ReNcell CX cells, which promotes neuronal differentiation by activated AKT/GSK-3β/β-catenin pathways. A further mechanistic study indicated that the electron density of the surface Ce atoms changed continuously with different crystal facets, which led to their different CAT-like activity and modulation of redox homeostasis in NPCs. Altogether, the different surface chemistry and atomic architecture of active sites on CeO 2 exert modulation of redox homeostasis and the fate of NPCs.

Glutamate excitotoxicity is caused by dysfunctional glutamate transporters and plays an important role in the pathogenesis of Parkinson's disease (PD); however, the mechanisms that underlie the regulation of glutamate transporters in PD are still not fully elucidated. MicroRNAs(miRNA), which are abundant in astrocytes and neurons, have been reported to play key roles in regulating the translation of glutamate-transporter mRNA. In this study, we hypothesized that the miR-30a-5p contributes to the pathogenesis of PD by regulating the ubiquitin-mediated degradation of glutamate transporter 1 (GLT-1). We demonstrated that short-hairpin RNA-mediated knockdown of miR-30a-5p ameliorated motor deficits and pathological changes like astrogliosis and reactive microgliosis in a mouse model of PD (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice). Western blotting and immunofluorescent labeling revealed that miR-30a-5p suppressed the expression and function of GLT-1 in MPTP-treated mice and specifically in astrocytes treated with 1-methyl-4-phenylpyridinium (MPP + ) (cell model of PD). Both in vitro and in vivo , we found that miR-30a-5p knockdown promoted glutamate uptake and increased GLT-1 expression by hindering GLT-1 ubiquitination and subsequent degradation in a PKCα-dependent manner. Therefore, we conclude that miR-30a-5p represents a potential therapeutic target for the treatment of PD.

α-Synuclein (α-syn), a small highly conserved presynaptic protein containing 140 amino acids, is thought to be the main pathological hallmark in related neurodegenerative disorders. Although the normal function of α-syn is closely involved in the regulation of vesicular neurotransmission in these diseases, the underlying mechanisms of post-translational modifications (PTMs) of α-syn in the pathogenesis of Parkinson's disease (PD) have not been fully characterized. The pathological accumulation of misfolded α-syn has a critical role in PD pathogenesis. Recent studies of factors contributing to α-syn-associated aggregation and misfolding have expanded our understanding of the PD disease process. In this Review, we summarize the structure and physiological function of α-syn, and we further highlight the major PTMs (namely phosphorylation, ubiquitination, nitration, acetylation, truncation, SUMOylation, and O-GlcNAcylation) of α-syn and the effects of these modifications on α-syn aggregation, which may elucidate mechanisms for PD pathogenesis and lay a theoretical foundation for clinical treatment of PD.

Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common neurodegenerative disorders, with an overall global incidence of 40 million. Many studies have revealed the association of intestinal disorders and bacterial infections with PD, but few studies have found such a relationship with AD. In this meta-analysis, related articles published up to September 2018 were searched in PubMed. Of the 2121 related articles screened initially, 56 were found to be eligible. Data on the risks of PD and AD due to five intestinal disorders and infection with Helicobacter pylori , as a representative intestinal microbe, were obtained, and a fixed- or random-effects model was used to pool the odds ratios (ORs) with 95% confidence interval (CIs) from individual studies. The combined OR for all types of intestinal disorders with an increased risk of PD was 3.36 (95% CI: 2.70-4.17). The ORs for each category were as follows: constipation, 4.05 (95% CI, 3.24-5.06); inflammatory bowel disease (IBD), 1.16 (95% CI, 0.89-1.52); irritable bowel syndrome (IBS), 1.75 (95% CI, 0.55-5.56); small intestinal bacterial overgrowth, 5.15 (95% CI, 3.33-7.96); and diarrhea, 1.27 (95% CI, 0.28-5.75). The combined OR of all types of intestinal disorders with an increased risk of AD was 1.52 (95% CI, 1.09-2.13). The ORs for IBS and IBD were 1.42 (95% CI, 1.02-1.99) and 2.40 (95% CI, 1.00-5.76), respectively. The risk estimates of H. pylori infection in PD and AD patients were as follows: OR, 1.65 (95% CI, 1.43-1.91) and OR, 1.40 (95% CI, 1.12-1.76), respectively. These findings suggest that PD and AD are significantly associated with intestinal disorders. The negative roles of H. pylori in the development of PD or AD should be evaluated to shed new light on the diagnosis and treatment of PD and AD. National governments should periodically inspect the intestinal condition of residents and extend health plans to improve intestinal health to prevent potential neurological disorders.