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Background: Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been shown to be involved in Parkinson's disease (PD) progression, but its mechanism needs to be further explored., Methods: Mice were injected with 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD mice models, and BV2 cells were treated with lipopolysaccharides (LPS) to mimic PD cell models. MALAT1 expression and suppressor of cytokine signaling 3 (SOCS3) protein level were examined using quantitative real-time PCR and western blot, respectively. Cell functions were tested by cell counting kit 8 assay and flow cytometry. The interaction between MALAT1 and SOCS3 was confirmed using RNA pull-down and RIP assays., Results: MALAT1 was upregulated in MPTP-induced PD mice and LPS-induced BV2 cells. Silencing of MALAT1 increased viability, while inhibited apoptosis and inflammation in LPS-induced BV2 cells. Besides, MALAT1 enhanced the SOCS3 promoter methylation to decrease its expression by recruiting DNMT1, DNMT3A and DNMT3B. Furthermore, SOCS3 knockdown eliminated sh-MALAT1-mediated the inhibition effect on LPS-induced BV2 cell injury. In vivo, MALAT1 silencing ameliorated neurological impairment and neuroinflammation in MPTP-induced PD mice., Conclusion: Our data revealed that MALAT1 worsened PD processes via inhibiting SOCS3 expression by increasing its promoter methylation., (S. Karger AG, Basel.)

Background: LncRNAs perform a crucial impact on microglia's activation in Parkinson's disease (PD). Here, our purpose was to probe the function and involved mechanism of lncRNA SOX21-AS1 on microglial activation in PD., Methods: Mice were treated with MPTP, and BV2 cells were treated with LPS/ATP to build PD animal and cell models. Genes' expression was measured using RT-qPCR, immunoblotting, and IHC stain. ELISA was applied for testing inflammatory factors' levels. Cell viability and apoptosis were tested using kits. RIP and RNA pull-down assay were utilized for monitoring the bond of SOX21-AS1 to EZH2, and ChIP was applied for affirming the bond between EZH2 and SOCS3's promoter., Results: The expression of SOX21-AS1 and SOCS3 was abnormal in PD cell and animal models. Inhibition of SOX21-AS1 repressed LPS/ATP-induced activation in BV2 cells and nerve damage caused by activated BV2 cells, alleviating the pathological features of PD mice. Further studies found that SOX21-AS1 epigenetically inhibited SOCS3 by recruiting EZH2 to SOCS3 promoter. SOX21-AS1 overexpression partially offset the repressive impact of SOCS3 enhancement on BV2 cell activation and the protective effect on nerve cells., Conclusion: SOX21-AS1 enhances LPS/ATP-induced activation of BV2 cells and nerve damage caused by activated BV2 cells though recruiting EZH2 to SOCS3's promoter, thereby alleviating PD progression. Our research supplies new potential target for curing PD., (© 2024 S. Karger AG, Basel.)

Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.

Homeobox transcript antisense RNA (HOTAIR), has been associated with neuroprotective effects in Parkinson's disease (PD). However, the underlying mechanisms still remain unclear. Hence, this present study attempted to clarify the functional relevance of HOTAIR in PD. We established an in vivo mouse model of PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and an in vitro cell model of PD by treating dopaminergic neuron MN9D cells with 1-methyl-4-phenylpyridinium species (MPP + ). The expressions of somatostatin receptor 1 (SSTR1) and HOTAIR were altered to examine their effects on MN9D cell viability and apoptosis, as well as on movement impairments in MPTP-induced PD mouse model. The results indicated that HOTAIR expression was upregulated and SSTR1 was downregulated in in vivo and in vitro PD models. HOTAIR could bind to the promoter region of SSTR1, resulting in an increase of SSTR1 methylation through the recruitment of DNA methyltransferases in PD cell models. Notably, overexpression of HOTAIR and silencing of SSTR1 enhanced dopaminergic neuron apoptosis in MN9D cells and exacerbated dyskinesia in MPTP-induced PD mouse model. Collectively, overexpressed HOTAIR stimulates DNA methylation of SSTR1 to reduce SSTR1 expression, thereby accelerating dyskinesia and facilitating dopaminergic neuron apoptosis in a MPTP-lesioned PD mouse model via activation of the ERK1/2 axis., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

This study is conducted to investigate the role of lncRNA urothelial carcinoma-associated 1 (UCA1) in the protection of dopaminergic neurons in Parkinson's disease (PD) through regulating the PI3K/Akt signaling pathway. PD rat model was induced by injection of 6-hydroxydopamine (6-OHDA) to damage the substantia nigra striatum. The successfully modeled PD rats were introduced with siRNA-negative control (NC) or UCA1-siRNA. The expression of UCA1 in neurobehavioral change, neuroinflammatory response and oxidative stress of PD rats were explored. The effect of UCA1 on the PI3K/Akt signaling pathway and downstream proteins IκBα and ERK was also investigated. The rats with PD exhibited aggregated neurobehavioral change, increased neuroinflammatory response and oxidative stress. Down-regulation of UCA1 up-regulated the expression of TH positive cells and DA content, reduced the apoptosis of substantia nigra neurons, the apoptosis of substantia nigra neurons and oxidative stress and improved the neuroinflammatory response in PD rats. Down-regulation of UCA1 inhibited the activation of the PI3K/AKT signaling pathway in substantia nigra of PD rats. Our study suggests that the downregulated lncRNA UCA1 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in PD rats through the inhibition of the PI3K/Akt signaling pathway., (Copyright © 2019. Published by Elsevier B.V.)

Background: Prognostic significance of serum calcium level in patients with intracerebral hemorrhage is not well studied. The aim of the study was to identify if a relationship between admission serum calcium level and prognosis exists in patients with intracerebral hemorrhage., Methods: A total of 1262 confirmed intracerebral hemorrhage patients were included. Demographic data, medical history, medicine history, laboratory data, imaging data, clinical score, and progress note were collected from their medical records. All images of head computed tomography were reanalyzed. Ninety-day prognosis was recorded, and poor outcome was defined as death or major disability caused by intracerebral hemorrhage., Results: During the 90-day follow-up period, 504 patients died and 226 patients suffered from major disability. Death and major disability were combined as poor prognosis. The remaining 532 patients showed good prognosis. Admission serum calcium level was lower in the patients with poor prognosis than in the patients with good prognosis (2.41 ± 0.23 mmol/l, 2.55 ± 0.26 mmol/l, P < 0.001). Admission INR and hematoma volume were higher in the patients with poor prognosis than in the patients with good prognosis (INR: 1.74 ± 0.29, 1.70 ± 0.29, P = 0.029; hematoma volume: 11.6 ± 4.4 ml, 10.7 ± 4.1 ml, P < 0.001). There was no difference in admission APTT level between the two prognosis groups (28.4 ± 5.6 s, 27.8 ± 5.4 s, P = 0.056). A multivariate COX regression analysis reported that admission serum calcium level ≤ 2.41 mmol/l was associated with the increased risk of poor prognosis (death or major disability) in the patients (HR 1.45, 95% CI 1.32-1.60). In addition, there was a significant linear association of serum calcium level with coagulation function markers and hematoma volume on admission (APTT: r = - 0.091, P = 0.001; INR: r = - 0.063, P = 0.025; hematoma volume: r = -0.108, P < 0.001)., Conclusions: Admission serum calcium level might be a prognostic marker for intracerebral hemorrhage. Potential mechanism involved calcium-induced coagulation function abnormality.

Objective: This study aimed to analyze the hereditary spastic paraplegia (HSP)/spastic paraplegia 3A ( SPG3A ) genomic structure as well as the polymorphisms in SPG3G genomic structure by comparing with the normal subjects., Methods: A total of 66 sporadic cases with HSP were collected from April 2014 to September 2016. Genomic DNA extraction was performed, and all coding exons and junction region in the SPG3A gene were sequenced. Genetic mutations were identified and DNA sequence alignment was performed against 80 normal subjects without blood relationship. The polymorphism in SPG3A gene was analyzed., Results: The coding sequence of the SPG3A gene consisted of 14 exons and two polymorphisms were detected at exons 2 and 3 compared with the normal subjects; one polymorphism was detected at exons 3, 4 and 6, respectively., Conclusion: The two coding exons in the SPG3A gene in normal subjects were polymorphic and highly conservative. The intron consisted of 3 polymorphic coding sequences. Understanding the polymorphism and genetic mutations in the SPG3A gene will contribute to the diagnosis and treatment of HSP., Competing Interests: None., (IJCEP Copyright © 2017.)

The PLA2G6 gene encodes a group VIA calcium-independent phospholipase A(2), and has been suggested as the causative gene for autosomal recessive dystonia-parkinsonism. We conducted a case-control study using 531 mainland Chinese Parkinson's disease (PD) patients and 561 healthy controls, and genotyped 4 tag single nucleotide polymorphisms (SNPs) of the PLA2G6 gene: rs4375, rs2267369, rs132985, and rs2284063. Logistic regression analysis revealed no difference in genotype or allele frequencies for any of the SNPs between the sporadic PD group and control group. Similarly, comparison of SNPs in patients with either early-onset (EOPD, ≤ 50 years) or late-onset (>50 years) PD revealed no statistical differences from controls. We detected no significant association of the 4 SNPs with PD at the genotypic level, after adjustment for age. The rs132985 genotype frequency showed a difference in male patients but not in female patients, but the P value did not survive Bonferroni correction (Pcorr = 0.068). We found that the rs132985 A-rs2284063 C haplotype is marginally associated with increased risk of developing PD (P = 0.048) after 10,000 permutations. These findings suggest that PLA2G6 is not a susceptibility gene for PD in our population. However, a broader examination and a replication of this study in other populations are needed., (Copyright © 2012 Elsevier Ltd. All rights reserved.)