Backgroundα-Synuclein (α-Syn), a pathological hallmark of Parkinson’s disease (PD), has been recognized to induce the production of interleukin-1β in a process that depends, at least in vitro, on nod-like receptor protein 3 (NLRP3) inflammasome in monocytes. However, the role of NLRP3 inflammasome activation in the onset of PD has not yet been fully established.ResultsIn this study, we showed that NLRP3 inflammasomes were activated in the serum of PD patients and the midbrain of PD model mice. We further clarified that α-syn activated the NLRP3 inflammasome through microglial endocytosis and subsequent lysosomal cathepsin B release. Deficiency of caspase-1, an important component of NLRP3 inflammasome, significantly inhibited α-syn-induced microglia activation and interleukin-1β production, which in turn alleviated the reduction of mesencephalic dopaminergic neurons treated by microglia medium. Specifically, we demonstrated for the first time that Nlrp3 is a target gene of microRNA-7 (miR-7). Transfection of miR-7 inhibited microglial NLRP3 inflammasome activation whereas anti-miR-7 aggravated inflammasome activation in vitro. Notably, stereotactical injection of miR-7 mimics into mouse striatum attenuated dopaminergic neuron degeneration accompanied by the amelioration of microglial activation in MPTP-induced PD model mice.ConclusionsOur study provides a direct link between miR-7 and NLRP3 inflammasome-mediated neuroinflammation in the pathogenesis of PD. These findings will give us an insight into the potential of miR-7 and NLRP3 inflammasome in terms of opening up novel therapeutic avenues for PD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13024-016-0094-3) contains supplementary material, which is available to authorized users.

This study assessed the patterns of functional and structural connectivity abnormalities in patients with Parkinson's disease with freezing of gait (PD FOG+) compared with those without freezing (PD FOG-) and healthy controls (HCs). Resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI) scans were obtained from 14 PD FOG+, 16 PD FOG- and 16HCs. Between-group difference in pedunculopontine nucleus (PPN) functional connectivity (FC) was performed to assess FC dysfunction. Tract-based spatial statistics (TBSS) was applied to compare white matter (WM) impairment across the whole brain between groups. PD FOG+ patients exhibited abnormal PPN FC, compared with HCs and with PD FOG-, mainly in the corticopontine-cerebellar pathways (in the bilateral cerebellum and in the pons), as well as the visual temporal areas (in the right middle temporal gyrus and in the right inferior temporal gyrus). Moreover, PD FOG+ patients, showed more pronounced WM abnormalities, relative to controls, including the interhemispheric connections of corpus callosum, the cortico-cortical WM tracts of the cingulum, the superior longitudinal fasciculus and inferior fronto-occipital fasciculus, the corticofugal tract (cerebral peduncles, internal capsule, corona radiata), as well as tracts connecting the thalamus (thalamic radiation). This study suggests that FOG in PD is associated with abnormal PPN FC network, mainly affecting the corticopontine-cerebellar pathways as well as visual temporal areas involved in visual processing, and with diffuse WM deficits extending to motor, sensory and cognitive regions. Combining rs-fMRI and DTI method, our study should advance the understanding of neural mechanisms underlying FOG in PD.

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Lilium is a world famous fragrant bulb flower with high ornamental and economic values, and significant differences in fragrance are found among different Lilium genotypes. In order to explore the mechanism underlying the different fragrances, the floral scents of Lilium ‘Sibeia’, with a strong fragrance, and Lilium ‘Novano’, with a very faint fragrance, were collected in vivo using a dynamic headspace technique. These scents were identified using automated thermal desorption—gas chromatography/mass spectrometry (ATD-GC/MS) at different flowering stages. We used RNA-Seq technique to determine the petal transcriptome at the full-bloom stage and analyzed differentially expressed genes (DEGs) to investigate the molecular mechanism of floral scent biosynthesis. The results showed that a significantly higher amount of Lilium ‘Siberia’ floral scent was released compared with Lilium ‘Novano’. Moreover, monoterpenes played a dominant role in the floral scent of Lilium ‘Siberia’; therefore, it is believed that the different emissions of monoterpenes mainly contributed to the difference in the floral scent between the two Lilium genotypes. Transcriptome sequencing analysis indicated that ~29.24 Gb of raw data were generated and assembled into 124,233 unigenes, of which 35,749 unigenes were annotated. Through a comparison of gene expression between these two Lilium genotypes, 6,496 DEGs were identified. The genes in the terpenoid backbone biosynthesis pathway showed significantly different expression levels. The gene expressions of 1-deoxy-D-xylulose 5-phosphate synthase (DXS), 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), 4-hydroxy-3-methylbut-2-enyl diphosphate synthase (HDS), 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (HDR), isopentenyl diphosphate isomerase (IDI), and geranyl diphosphate synthase (GPS/GGPS), were upregulated in Lilium ‘Siberia’ compared to Lilium ‘Novano’, and two monoterpene synthase genes, ocimene synthase gene (OCS) and myrcene synthase gene (MYS), were also expressed at higher levels in the tepals of Lilium ‘Siberia’, which was consistent with the monoterpene release amounts. We demonstrated that the high activation levels of the pathways contributed to monoterpene biosynthesis in Lilium ‘Siberia’ resulting in high accumulations and emissions of monoterpenes, which led to the difference in fragrance between these two Lilium genotypes.

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