Tyramine receptors (TARs) can be activated by tyramine (TA) or octopamine (OA) and have been shown to be related to physiological regulation (e.g., gustatory responsiveness, social organization, and learning behavior) in a range of insect species. A tyramine receptor gene in Plutella xylostella, Pxtar1, was cloned and stably expressed in the HEK-293 cell line. Pharmacological properties and expression profile of Pxtar1 were also analyzed. Tyramine could activate the PxTAR1 receptor, increasing the intracellular Ca2+ concentration ((Ca2+)i) at an EC50 of 13.1 nM and reducing forskolin (10 μM)-stimulated intracellular cAMP concentration ((cAMP)i) at an IC50 of 446 nM. DPMF (a metabolite of amitraz) and L(-)-carvone (an essential oil) were found to act as PxTAR1 receptor agonists. Conversely, yohimbine and mianserin had significant antagonistic effects on PxTAR1. In both larvae and adults, Pxtar1 had the highest expression in the head capsule and expression of Pxtar1 was higher in male than in female reproductive organs. This study reveals the temporal and spatial differences and pharmacological properties of Pxtar1 in P. xylostella and provides a strategy for screening insecticidal compounds that target PxTAR1.

Background: Statins have key lipid-lowering, anti-inflammatory, and anti-oxidative effects. However, it remains unclear whether statins are beneficial to patients with Parkinson's disease (PD). This study aimed to evaluate the relationship between statins and PD through a systematic review. Methods: This study adhered to the guideline of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Potentially relevant case-control or cohort studies published before March 2018 were identified by searching the MEDLINE (PubMed), EMBASE (OVID), CENTRAL (Cochrane Library), CNKI, WANGANG, VIP, CBM, CMCC, Clinicaltrials.gov, ProQuest, Opengray, and ISI Proceedings databases and conducting a manual search. Summarized relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a fixed effect model. Sensitivity and subgroup analyses were also performed. Results: The meta-analysis included 17 studies (3,845,303 patients; 8 case-control and 9 cohort studies), including 5 articles not cited by other studies. We searched the Chinese database, but unfortunately, no Chinese literature can be included in the study. Briefly, statins could decrease the risk of PD, with a summary OR of 0.92 (95% CI: 0.86–0.99). A sensitivity analysis demonstrated the robustness of the results. Subgroup analyses revealed heterogeneity across the studies in terms of subject race, study type, reporting style, quality, statins type, and time for taking statins. Conclusion: Our study provides evidence that statins, especially atorvastatin, can reduce the risk of PD. Different time of statins using has different effects on PD. However, additional randomized controlled trials and observational studies are needed to confirm this conclusion. Registration Id: PROSPERO CRD: 42018095580

The progression of Parkinson’s disease (PD) is often accompanied by the loss of substantia nigra dopaminergic neurons, mitophagy damage, learning, and memory impairment. Idebenone is a therapeutic drug that targets the mitochondria of neurodegenerative diseases, but its role in Parkinson’s disease and its pathological mechanism are still unclear. The purpose of this study was to investigate whether idebenone could improve behavioral disorders, especially motor, learning, and memory disorders, in mouse PD models and to explore its molecular mechanism. In the present study, C57BL-6 mice underwent intraperitoneal injection of MPTP (30 mg/kg) once a day for five consecutive days. Then, a 200 mg/kg dose was given as a single daily gavage of idebenone dissolved in water for 21 days after the successful establishment of the subacute MPTP model. Motor, learning, and memory were measured by a water maze and a rotarod test. Our results showed that idebenone could reduce MPTP-induced dopaminergic neuron damage and improve movement disorders, memory, and learning ability, which may be associated with upregulating mitochondrial autophagy-related outer membrane proteins VDAC1 and BNIP3 and activating the Parkin/PINK1 mitochondrial autophagy pathway. To confirm whether idebenone promotes the smooth progression of autophagy, we used eGFP-mCherry-LC3 mice to construct a subacute model of Parkinson’s disease and found that idebenone can increase autophagy in dopaminergic neurons in Parkinson’s disease. In summary, our results confirm that idebenone can regulate the expression of the mitochondrial outer membrane proteins VDAC1 and BNIP3, activate Parkin/PINK1 mitophagy, promote the degradation of damaged mitochondria, reduce dopaminergic neuron damage, and improve behavioral disorders in Parkinson’s disease mice.

Parkinson’s disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons. It is characterized by static tremors, stiffness, slow movements, and gait disturbances, but it is also accompanied by anxiety and depression. Our previous study showed that atorvastatin could reduce the risk of PD, but the mechanism is still unclear. In this paper, Our findings showed that atorvastatin increased muscle capacity and the coordination of movement and improved anxiety and depression. Atorvastatin could decrease the expression of α-synuclein Ser129 and NADPH oxidase 2 (NOX2), increase the protein expression of LC3II/I, and promote autophagy flow. To further confirm that atorvastatin protection was achieved by inhibiting NOX2, we injected at midbrain with NOX2 shRNA (M) lentivirus and found that silent NOX2 produced the same effect as atorvastatin. Further research found that atorvastatin could reduce MPTP-induced oxidative stress damage, while inhibiting NOX2 decreased the antioxidative stress effect of atorvastatin. Our results suggest that atorvastatin can improve muscle capacity, anxiety and depression by inhibiting NOX2, which may be related to NOX2-mediated oxidative stress and autophagy. Atorvastatin may be identified as a drug that can effectively improve behavioral disorders. NOX2 may be a potential gene target for new drug development in PD.

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Neuroinflammation and oxidative stress play key roles in the pathological development of Parkinson's disease (PD). Nerve growth factor-induced gene B (Nur77) is closely related to dopamine neurotransmission, and its pathogenesis is unclear. This study aims to investigate the role and mechanism of Nur77 in a cell model of Parkinson's disease. Silencing Nur77 with siRNA can aggravate intracellular LDH release, increase the expression of pro-inflammatory genes (such as tumor necrosis factor α, nuclear factor κB (p65), monocyte chemotactic protein 1, interleukin-6), and decrease cell survival, decrease expression of nuclear factor E2-related factor(Nrf2), heme oxygenase 1, NADPH quinineoxidoreductase-1. Cytosporone B (Nur77 agonist) has the opposite effect to Nur77 silencing. PDTC (NF-κB inhibitor / antioxidant) can also inhibit pro-inflammatory genes to a similar degree as Cytosporone B. Phosphorylated IκB-α can be inhibited by Cytosporone B, while silencing Nur77 can increase the protein expression level of phosphorylated IκB-α. After silencing IκB-α, both Cytosporone B and siNur77 did not affect pro-inflammatory genes and antioxidant stress. These findings reveal the first evidence that Nur77 exerts anti-inflammatory and antioxidant stress effects by inhibiting IκB-α phosphorylation expression in a Parkinson cell model. Nur77 may be a potential therapeutic target for Parkinson's disease.

Background Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. The oxidative stress is an important component of the pathogenesis of PD. Artemisinin (ART) has antioxidant and neuroprotective effects. The purpose of this study is to explore the neuroprotective effect of ART on 1-methyl-4-phenyliodine iodide (MPP +)-treated SH-SY5Y cells and underlying mechanism. Methods We used MPP+-treated SH-SY5Y cells to study the neuroprotective effect of ART. Cell viability was measured by MTT assay after incubating the cells with MPP+ and/or ART for 24 h. DCFH-DA was used to detect the level of intracellular reactive oxygen species (ROS), and WST-8 was used to detect the level of superoxide dismutase (SOD). The level of intracellular reduced glutathione (GSH) was detected with 5,5΄-dithiobis-(2-nitrobenzoic acid), and the level of malondialdehyde (MDA) was assessed based on the reaction of MDA and thiobarbituric acid. A mitochondrial membrane potential detection kit (JC-1) was used to detect changes in the mitochondrial membrane potential (MMP), and an Annexin V-FITC cell apoptosis kit was used to detect cell apoptosis. The expression levels of caspase-3, cleaved caspase-3 and the autophagy-related proteins LC3, beclin-1, and p62 were detected by Western blotting. In addition, to verify the change in autophagy, we used immunofluorescence to detect the expression of LC3 and p62. Results No significant cytotoxicity was observed at ART concentrations up to 40 μM. ART could significantly increase the viability of SH-SY5Y cells treated with MPP+ and reduce oxidative stress damage and apoptosis. In addition, the Western blotting and immunofluorescence results showed that MPP+ treatment could increase the protein expression of beclin1 and LC3II/LC3I and decrease the protein expression of p62, indicating that MPP+ treatment could induce autophagy. Simultaneous treatment with ART and MPP+ could decrease the protein expression of beclin1 and LC3II/LC3I and increase the protein expression of p62, indicating that ART could decrease the level of autophagy induced by MPP+. Conclusion Our results indicate that ART has a protective effect on MPP+-treated SH-SY5Y cells by the antioxidant, antiapoptotic activities and inhibition of autophagy. Our findings may provide new hope for the prevention and treatment of PD.

In insects, inward-rectifying potassium (Kir) channels regulate vital physiological functions, such as feeding behavior, silk secretion, renal excretion, and immune function. Therefore, they offer promising potential as targets for insecticides. Three types of Kir subunits have been identified in Diptera and Hemiptera, but the Kir subunits of Lepidoptera still remain unclear. This study identified five Kir subunit genes (pxkir1, pxkir2, pxkir3A, pxkir3B, and pxkir4) in the transcriptome of Plutella xylostella. Phylogenetic analysis identified pxkir1, pxkir2, pxkir3A, and pxkir3B as orthologous genes of kir1–3 in other insects. Interestingly, pxkir4 may be encoding a new class of Kir subunit in Lepidoptera that has not been reported to date. To identify further Kir channel subunits of P. xylostella, the gene expression profiles of five pxkir genes were studied by quantitative real-time PCR. These pxkir genes are expressed throughout the development of P. xylostella. pxkir1 and pxkir2 were highly expressed in thoraxes and legs, while pxkir3 (3A and 3B) and pxkir4 had high expression levels in the midgut and Malpighian tubules. This study identified the composition and distribution of Kir subunits in P. xylostella for the first time, and provides useful information for the further study of Kir channel subunits in Lepidoptera.