Iron deposition in subcortical nuclei of Parkinson's disease: A meta-analysis of quantitative iron-sensitive magnetic resonance imaging studies.

BACKGROUND: Iron deposition plays a crucial role in the pathophysiology of Parkinson's disease (PD), yet the distribution pattern of iron deposition in the subcortical nuclei has been inconsistent across previous studies. We aimed to assess the difference patterns of iron deposition detected by quantitative iron-sensitive magnetic resonance imaging (MRI) between patients with PD and patients with atypical parkinsonian syndromes (APSs), and between patients with PD and healthy controls (HCs). METHODS: A systematic literature search was conducted on PubMed, Embase, and Web of Science databases to identify studies investigating the iron content in PD patients using the iron-sensitive MRI techniques (R2* and quantitative susceptibility mapping [QSM]), up until May 1, 2023. The quality assessment of case-control and cohort studies was performed using the Newcastle-Ottawa Scale, whereas diagnostic studies were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Standardized mean differences and summary estimates of sensitivity, specificity, and area under the curve (AUC) were calculated for iron content, using a random effects model. We also conducted the subgroup-analysis based on the MRI sequence and meta-regression. RESULTS: Seventy-seven studies with 3192 PD, 209 multiple system atrophy (MSA), 174 progressive supranuclear palsy (PSP), and 2447 HCs were included. Elevated iron content in substantia nigra (SN) pars reticulata (P <0.001) and compacta (P <0.001), SN (P <0.001), red nucleus (RN, P <0.001), globus pallidus (P <0.001), putamen (PUT, P = 0.009), and thalamus (P = 0.046) were found in PD patients compared with HCs. PD patients showed lower iron content in PUT (P <0.001), RN (P = 0.003), SN (P = 0.017), and caudate nucleus (P = 0.027) than MSA patients, and lower iron content in RN (P = 0.001), PUT (P <0.001), globus pallidus (P = 0.004), SN (P = 0.015), and caudate nucleus (P = 0.001) than PSP patients. The highest diagnostic accuracy distinguishing PD from HCs was observed in SN (AUC: 0.85), and that distinguishing PD from MSA was found in PUT (AUC: 0.90). In addition, the best diagnostic performance was achieved in the RN for distinguishing PD from PSP (AUC: 0.84). CONCLUSION: Quantitative iron-sensitive MRI could quantitatively detect the iron content of subcortical nuclei in PD and APSs, while it may be insufficient to accurately diagnose PD. Future studies are needed to explore the role of multimodal MRI in the diagnosis of PD. REGISTRISION: PROSPERO; CRD42022344413.

Efficacy and safety of salbutamol in treatment of children with later-onset spinal muscular atrophy. / ç¡«é ¸æ²™ä¸èƒºé†‡æ²»ç–—æ™šå‘åž‹è„Šé«“æ€§è‚ŒèŽç¼©ç—‡æ‚£å„¿ä¸´åºŠç–—æ•ˆåŠå®‰å ¨æ€§è§‚å¯Ÿ.

OBJECTIVES: To investigate the clinical efficacy and safety of salbutamol in the treatment of children with later-onset spinal muscular atrophy (SMA). METHODS: This study is a prospective single-arm phase Ⅲ clinical study. Pediatric patients with SMA type Ⅱ and Ⅲ who visited Department of Neurology, Children's Hospital, Zhejiang University School of Medicine from December 2020 to June 2022 were enrolled. All patients were evaluated with motor function scales, pulmonary function test and drug safety before study. Patients were treated with salbutamol tablets orally, with an initial dose of 1 mg (tid). If tolerable, the dose was increased to 1.5 mg (tid) in the second week, then increased to 2 mg (tid) from the third week and maintained for 6 months. Patients were followed up at 1, 3 and 6 months of treatment. RESULTS: Twenty-six patients were enrolled, including 10 boys and 16 girls. There were 16 cases of SMA type Ⅱ and 10 cases of type Ⅲ with age at treatment initiation of 5.67 (3.13, 7.02) years and disease duration of 2.54 (1.31, 4.71) years. The Hammersmith Functional Motor Scale-Expanded (HFMSE) scores were increased from 14.0 (6.5, 43.0) before treatment to 26.0 (15.0, 46.5) after treatment (Z=－4.144, P<0.01) in 25 cases. The Revised Upper Limb Module Scale scores were increased from 33.0 (25.5, 36.0) before treatment to 35.0 (31.0, 36.5) after treatment (Z=－2.214, P<0.05) in 9 cases. In 7 ambulant children with SMA type Ⅲ, the six minutes walking distance was increased by 30 (15, 52) m after a 6-month treatment (Z=－2.366, P<0.05). Compared with the baseline pulmonary functions the patients showed a significant increase in forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF) in 15 cases after treatment (all P<0.05). According to patients and caregivers subjective reporting, there were various degrees of improvement in coughing, sputum production ability and exercise endurance. No serious adverse events were observed during the study. CONCLUSIONS: Short-term oral administration of salbutamol may improve motor and pulmonary functions in later-onset SMA children with good safety.

Feasibility analysis of intrathecal administration strategy of nusinersen based on Cobb angle in children with spinal muscular atrophy.

AIM: This retro-prospective observational study described the experience in lumbar puncture procedures in children with spinal muscular atrophy (SMA) with and without neuromuscular scoliosis in a single center. The technical feasibility of intrathecal nusinersen administration was the main limiting factor. STUDY DESIGN: A total of 457 technically successful intrathecal injections based on a hierarchical strategy in Cobb angle were reviewed in 81 SMA children aged 0.75-13.5 years who were referred for nusinersen injections in our hospital from October 2019 to December 2022. RESULTS: Under local anesthesia, conventional lumbar puncture was performed on 47 patients without spinal deformity (Cobb angle of 0-10°) and 20 patients with moderate scoliosis (Cobb angle of 10-50°). Ultrasound-assisted lumbar puncture was performed on 12 patients with moderate scoliosis but lordosis. A combination of ultrasound imaging and three-dimensional CT under sedation was performed in the remaining 14 patients with severe scoliosis (Cobb angle >50°). No severe complications were found. CONCLUSION: Cobb angle is an important basis for intrathecal administration of nusinersen. It is feasible and suitable to carry out intrathecal nusinersen injection under ultrasound combined with three-dimensional CT imaging for children with severe scoliosis.

Tau-PET imaging in Parkinson's disease: a systematic review and meta-analysis.

Background: Pathological tau accumulates in the cerebral cortex of Parkinson's disease (PD), resulting in cognitive deterioration. Positron emission tomography (PET) can be used for in vivo imaging of tau protein. Therefore, we conducted a systematic review and meta-analysis of tau protein burden in PD cognitive impairment (PDCI), PD dementia (PDD), and other neurodegenerative diseases and explored the potential of the tau PET tracer as a biomarker for the diagnosis of PDCI. Methods: PubMed, Embase, the Cochrane Library, and Web of Science databases were systematically searched for studies published till 1 June 2022 that used PET imaging to detect tau burden in the brains of PD patients. Standardized mean differences (SMDs) of tau tracer uptake were calculated using random effects models. Subgroup analysis based on the type of tau tracers, meta-regression, and sensitivity analysis was conducted. Results: A total of 15 eligible studies were included in the meta-analysis. PDCI patients (n = 109) had a significantly higher tau tracer uptake in the inferior temporal lobe than healthy controls (HCs) (n = 237) and had a higher tau tracer uptake in the entorhinal region than PD with normal cognition (PDNC) patients (n = 61). Compared with progressive supranuclear palsy (PSP) patients (n = 215), PD patients (n = 178) had decreased tau tracer uptake in the midbrain, subthalamic nucleus, globus pallidus, cerebellar deep white matter, thalamus, striatum, substantia nigra, dentate nucleus, red nucleus, putamen, and frontal lobe. Tau tracer uptake values of PD patients (n = 178) were lower than those of patients with Alzheimer's disease (AD) (n = 122) in the frontal lobe and occipital lobe and lower than those in patients with dementia with Lewy bodies (DLB) (n = 55) in the occipital lobe and infratemporal lobe. Conclusion: In vivo imaging studies with PET could reveal region-specific binding patterns of the tau tracer in PD patients and help in the differential diagnosis of PD from other neurodegenerative diseases. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/.

The Alterations of Gut Microbiome and Lipid Metabolism in Patients with Spinal Muscular Atrophy.

INTRODUCTION: Spinal muscular atrophy (SMA) can cause multiple system dysfunction, especially lipid metabolic disorders, for which management strategies are currently lacking. Microbes are related to metabolism and the pathogenesis of neurological diseases. This study aimed to preliminarily explore the alterations in the gut microbiota in SMA and the potential relationship between altered microbiota and lipid metabolic disorders. METHODS: Fifteen patients with SMA and 17 gender- and age-matched healthy controls were enrolled in the study. Feces and fasting plasma samples were collected. 16S ribosomal RNA sequencing and nontargeted metabolomics analysis were performed to explore the correlation between microbiota and differential lipid metabolites. RESULTS: No significant difference was found in microbial diversity (α- and ß-diversity) between the SMA and control groups, with both groups having a relatively similar community structure. However, compared to the control group, the SMA group showed an increased relative abundance of the genera Ruminiclostridium, Gordonibacter, Enorma, Lawsonella, Frisingicoccus, and Anaerofilum and a decreased abundance of the genera Catabacter, Howardella, Marine_Methylotrophic_Group_3, and Lachnospiraceae_AC2044_group. The concurrent metabolomic analysis showed that the SMA group had 56 different kinds of lipid metabolite levels than did the control group. Additionally, the Spearman correlation suggested a correlation between the altered differential lipid metabolites and the above-mentioned altered microbiota. CONCLUSIONS: The gut microbiome and lipid metabolites differed between the patients with SMA and the control subjects. The altered microbiota may be related with the lipid metabolic disorders in SMA. However, further study is necessary to clarify the mechanism of lipid metabolic disorders and develop management strategies to improve the related complications in SMA.

Remote scoring models of rigidity and postural stability of Parkinson's disease based on indirect motions and a low-cost RGB algorithm.

Background and objectives: The Movement Disorder Society's Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) is mostly common used for assessing the motor symptoms of Parkinson's disease (PD). In remote circumstances, vision-based techniques have many strengths over wearable sensors. However, rigidity (item 3.3) and postural stability (item 3.12) in the MDS-UPDRS III cannot be assessed remotely since participants need to be touched by a trained examiner during testing. We developed the four scoring models of rigidity of the neck, rigidity of the lower extremities, rigidity of the upper extremities, and postural stability based on features extracted from other available and touchless motions. Methods: The red, green, and blue (RGB) computer vision algorithm and machine learning were combined with other available motions from the MDS-UPDRS III evaluation. A total of 104 patients with PD were split into a train set (89 individuals) and a test set (15 individuals). The light gradient boosting machine (LightGBM) multiclassification model was trained. Weighted kappa (k), absolute accuracy (ACC ± 0), and Spearman's correlation coefficient (rho) were used to evaluate the performance of model. Results: For model of rigidity of the upper extremities, k = 0.58 (moderate), ACC ± 0 = 0.73, and rho = 0.64 (moderate). For model of rigidity of the lower extremities, k = 0.66 (substantial), ACC ± 0 = 0.70, and rho = 0.76 (strong). For model of rigidity of the neck, k = 0.60 (moderate), ACC ± 0 = 0.73, and rho = 0.60 (moderate). For model of postural stability, k = 0.66 (substantial), ACC ± 0 = 0.73, and rho = 0.68 (moderate). Conclusion: Our study can be meaningful for remote assessments, especially when people have to maintain social distance, e.g., in situations such as the coronavirus disease-2019 (COVID-19) pandemic.

Tau PET imaging in progressive supranuclear palsy: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the difference of tau burden between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs) or other neurodegenerative diseases using tau-positron emission tomography (PET) imaging. METHODS: A systematic search on PubMed, Embase, and Web of Science databases was performed for tau-PET studies in PSP patients, up to April 1, 2022. Standardized mean differences (SMDs) of tau tracer uptake were calculated using random-effects models. Subgroup analysis based on the type of tau tracers, meta-regression, and sensitivity analysis were conducted. RESULTS: Twenty-seven studies comprising 553 PSP, 626 HCs, and 406 other neurodegenerative diseases were included. Compared with HCs, PSP patients showed elevated tau binding in basal ganglia, midbrain, dentate nucleus, cerebellar white matter, and frontal lobe with decreasing SMD (SMD: 0.390-1.698). Compared with Parkinson's disease patients, increased tau binding was identified in the midbrain, basal ganglia, dentate nucleus, and frontal and parietal lobe in PSP patients with decreasing SMD (SMD: 0.503-1.853). PSP patients showed higher tau binding in the subthalamic nucleus (SMD = 1.351) and globus pallidus (SMD = 1.000), and lower binding in the cortex and parahippocampal gyrus than Alzheimer's disease patients (SMD: - 2.976 to - 1.018). PSP patients showed higher midbrain tau binding than multiple system atrophy patients (SMD = 1.269). CONCLUSION: Tau PET imaging indicates different topography of tau deposition between PSP patients and HCs or other neurodegenerative disorders. The affinity and selectivity of tracers for 4R-tau and the off-target binding of tracers should be considered when interpreting the results.

Prevalence of axial postural abnormalities and their subtypes in Parkinson's disease: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Axial postural abnormalities, mainly involving the spinal deformities, are disabling symptoms of Parkinson's disease (PD). However, the prevalence of axial postural abnormalities in PD and their clinical correlates remain unclear. The present study aimed to conduct a systematic review and meta-analysis of the prevalence of overall and subtypes of axial postural abnormalities in PD. METHODS: PubMed, Embase, Web of Science and Cochrane databases were searched up to 31st March, 2022. We identified studies that reported the prevalence of axial postural abnormalities in PD. The pooled estimate of prevalence was calculated using a random effect model. Subgroup analysis and meta-regression were performed. RESULTS: There were 19 studies met the inclusion criteria. The overall prevalence of axial postural abnormalities in PD was 22.1% (95% CI 19.7-24.5%). The prevalence of each subtype of axial postural abnormalities was 19.6% for scoliosis (95% CI 10.6-28.7%), 10.2% for camptocormia (95% CI 7.7-12.7%), 8% for Pisa syndrome (95% CI 4.7-11.4%), and 7.9% for antecollis (95% CI 3.9-11.9%). Subgroup analysis showed that the measuring method of axial postural abnormalities exerted significant effects on prevalence estimates. Axial postural abnormalities in PD were associated with older age, longer disease duration, higher H-Y stage, greater levodopa equivalent daily dose, more severe motor symptoms, motor fluctuations, and akinetic-rigid subtype. CONCLUSIONS: Axial postural abnormalities, which include scoliosis, camptocormia, Pisa syndrome, and antecollis, are not uncommon in patients with PD. Future research on axial postural abnormalities should be based on uniform diagnostic criteria and measuring methods.

Research on the Effect of Nursing Methods for Gestational Diabetes Mellitus Based on Comprehensive Nursing Intervention.

In order to explore the effective way of gestational diabetes care, this paper applies comprehensive nursing to gestational diabetes care. In terms of nursing intervention for pregnant women with gestational diabetes mellitus, combining the phased changes of pregnant women's physiological and psychological needs during pregnancy, this paper comprehensively implements health education, diet intervention, exercise intervention, pregnancy monitoring, psychological intervention, infection prevention, and perinatal monitoring and other nursing interventions in a selective and focused manner. This makes the intervention measures at each stage focused, intersecting, interpenetrating, and continuing to play a role, which can effectively improve the implementation effect of the intervention measures and better promote the effective improvement of pregnancy outcomes. In addition, this paper studies the effect of gestational diabetes care based on comprehensive nursing intervention through a controlled trial, and the study verifies that comprehensive nursing has a good effect in gestational diabetes care.

Evaluation of the relationship between SORL1 gene polymorphism and Parkinson's disease in the Chinese population.

OBJECTIVE: There is increasing evidence that lysosomal pathway dysfunction is closely linked to the pathogenesis of Parkinson's disease (PD). Considering the relationship between sortilin-related receptor 1 (SORL1) and lysosomal dysfunction, the abnormal aggregation of misfolded proteins in neurodegenerative disorders, especially in PD, and that glial cell-derived neurotrophic factor (GDNF) is the most effective neurotrophic factor affecting the activity of the dopamine system, and that SORL1 may induce PD by affecting GDNF, we investigated the correlation between three genetic variants (rs1010159, rs1629493, and rs2298813) of SORL1 gene polymorphisms and the risk of PD in the northern Chinese population in order to broaden the perspective for PD therapy. METHODS: Three single-nucleotide polymorphisms (SNPs) of SORL1 genes (rs1010159, rs1629493, and rs2298813) were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) on the DNA of 400 patients with PD and 400 healthy controls matched by age and gender. The chi-square test was used to analyze the statistical differences in genotypic and allelic polymorphism frequency between PD patients and healthy controls. Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to estimate potential correlations. RESULTS: The frequencies of the T allele of rs1010159 and the A allele of rs2298813 in patients with PD were much higher than those in the controls (P = 0.003, P = 0.042, respectively). For rs1010159, subgroup analysis showed statistical changes in the frequency of the T allele in all subgroups (P = 0.021, P = 0.036, P = 0.001, P = 0.030, respectively); however, genotypic frequency distributions were statistically significant only between male patients with PD and matched healthy male controls (P = 0.001), and between early onset PD (EOPD) and late-onset PD (LOPD) and controls (P = 0.001, P = 0.001). For rs2298813, the explicit model showed that the GA + AA genotype had an increased risk of PD compared with the GG genotype (P = 0.020, OR = 1.518, 95% CI = 1.065-2.162), and the additive model showed that GA was also associated with a higher trend in PD compared with the GG genotype (P = 0.037, OR = 1.475, 95% CI = 1.024-2.125), and the allelic and genotypic frequencies of the LOPD were statistically different from those of the healthy group (P = 0.013, P = 0.044; respectively). No distinct correlation was found between rs1629493 and PD risk. The GAT haplotype, together with the AGT haplotype, was associated with PD susceptibility. CONCLUSIONS: The rs1010159 and rs2298813 polymorphisms of the SORL1 gene rather than the rs1629493 polymorphism may be implicated in the susceptibility to PD in the northern Chinese population. Studies in different ethnicities and larger populations are indispensable for understanding the intrinsic correlation between the SORL1 gene and PD pathogenesis.

Association of PGLYRP2 gene polymorphism and sporadic Parkinson's disease in northern Chinese Han population.

Gut inflammation is increasingly corroborated to take part in the pathogenesis of Parkinson's disease (PD). The PGLYRP2 gene has been proven to increase susceptibility to inflammatory bowel disease (IBD). The present study aimed to explore the genetic relationship between single nucleotide polymorphism (SNP) of the PGLYRP2 gene and the risk of sporadic PD in the Han population of northern China. The genotypes of the rs3813135 T/C, rs733731 C/T and rs892145 A/T polymorphisms of the PGLYRP2 gene in 400 Chinese Han patients with PD and 400 healthy age-and sex-matched individuals were identified by the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP) method. The results showed that the frequency of the rs892145 AT heterozygote significantly differed between the PD and control groups (OR = 1.459, 95%CI = 1.459-1.039, P = 0.029), as well as the early-onset PD and control groups (P = 0.024). The rs3813135 polymorphism yielded only one significant result: C allele was more common in the male PD group than in the male control group (P = 0.045). Conversely, no significant difference in the genotype frequency of rs733731 was found between the PD and control groups. Five common haplotypes were assessed, of which the TTA and TCA haplotypes were related to PD susceptibility. In summary, our results indicated that the PGLYRP2 gene is associated with sporadic PD in the Chinese Han population, in which the rs892145 AT heterozygote might increase the risk of PD and possibly the risk of early-onset PD. Moreover, linkage disequilibrium (LD) analysis showed these three PGLYRP2 polymorphisms has a strong linkage in causing mutations.

Serum neurofilament light chain in adult and pediatric patients with myelin oligodendrocyte glycoprotein antibody-associated disease: Correlation with relapses and seizures.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) causes major disability as a consequence of recurrent demyelinating events and neuronal loss. Biomarkers identifying different phenotypes of recurrence or tissue damage might be useful to guide individualized therapy. Herein, we evaluated serum neurofilament light chain (sNfL) as a potential biomarker in both adult and pediatric MOGAD patients. Forty-nine patients with MOGAD (37 adults, 12 children) and 71 healthy controls (HCs) (56 adults, 15 children) were enrolled prospectively from September 2019 to April 2021 at the Third Affiliated Hospital of Sun Yat-sen University and the Children's Hospital, Zhejiang University School of Medicine. sNfL levels were determined using ultrasensitive single-molecule array assay and correlated with clinical parameters. The sNfL levels in MOGAD adults in a relapsed state (median: 31.0 pg/ml) were higher than those in a remission state (8.1 pg/ml, p = 0.001) and in HC adults (10.3 pg/ml, p = 0.004). Similar results were observed in children (relapse: 46.8 pg/ml vs. remission: 13.1 pg/ml, p = 0.001; and vs. HCs: 8.2 pg/ml, p = 0.007) sNfL levels were correlated with recent relapses within 60 days (multivariate: ß = 2.02, p = 0.003), seizures (multivariate: ß = 2.50, p = 0.021) and brain lesions on magnetic resonance imaging (MRI) of a recent relapse (multivariate: ß = 1.72, p = 0.012). Our study showed that sNfL levels are beneficial for identifying recent relapses and seizures and suggest that adult and pediatric MOGAD patients had similar sNfL levels.

CUB and Sushi Multiple Domains (CSMD1) Gene Polymorphisms and Susceptibilities to Idiopathic Parkinson's Disease in Northern Chinese Han Population: A Case-Control Study.

Evidence has shown that the CUB and Sushi Multiple Domains (CSMD1) gene is an inhibitor of the complement activation pathway and is also involved in central nervous system inflammation. Previous studies have revealed that the CSMD1 gene is related to familial Parkinson's disease. This study aimed to investigate the relationship between CSMD1 gene and susceptibility to Parkinson's disease in population of northern China. A case-control study was performed on 423 Parkinson's disease patients and 465 healthy controls matched for age and sex. DNA from enrolled subjects were extracted from the peripheral blood, and single nucleotide polymorphisms (SNPs) rs12681349 (C＞T), rs10503253 (C＞A), and rs1983474 (T＞G) within CSMD1 gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotype frequency of rs10503253 (CA versus CC : OR = 1.554, 95% CI = 1.169-2.066, p=0.002) and rs1983474 (GG versus TT : OR = 0.599, 95% CI = 0.401-0.895, p=0.012) was significantly different between PD cases and controls, but not for rs12681349. Comprehensive and subgroup analysis indicated that rs10503252 showed significant statistical differences in the dominant model (AA + CA versus CC : OR = 0.677, 95% CI = 0.517-0.886, p=0.004), late-onset cohort (CA versus CC : OR = 1.570, 95% CI = 1.159-2.126, p=0.004), and the female cohort (CA versus CC : OR = 0.687, 95% CI = 0.497-0.952, p=0.023), compared with the matched control group. The difference of recessive model of rs1983474 (GG versus TT + TG : OR = 1.837, 95% CI = 1.287-2.620, p=0.001) was significant in Parkinson's disease. According to the subgroup analysis, results indicated that late-onset cohort (GG versus TT : OR = 0.643, 95% CI = 0.420-0.985, p=0.042), male cohort (TG versus TT : OR = 2.160, 95% CI = 1.162-4.016, p=0.015), and female group (GG versus TT : OR = 0.418, 95% CI = 0.234-0.746, p=0.003) of rs1983474 were significantly associated with Parkinson's disease susceptibility. In both genotype and subgroup analysis, we failed to find any relationship between rs12681349 polymorphism and Parkinson's disease risk. Our results indicate that the rs10503253 and rs1983474 gene polymorphism may be associated with idiopathic Parkinson's disease susceptibility in Chinese population. Nevertheless, these conclusions need to be further verified by more studies.

Association between epidermal growth factor receptor gene polymorphisms and susceptibility to Parkinson's disease.

OBJECTIVE: The progressive loss of dopaminergic neurons in the mesencephalic substantia nigra is recognized as an important pathological feature of Parkinson's disease (PD). Several research studies have suggested that the EGFR signaling pathway may play a significant role in the survival and functional development of dopaminergic neurons. Therefore, genetic variations in these pathways may be related with PD susceptibility. The aim of our study was to explore the association between selected single nucleotide polymorphisms (SNPs) of the epidermal growth factor receptor (EGFR) gene, including rs730437, rs3752651 and rs11506105, and susceptibility to Parkinson's disease in a Han Chinese population. METHODS: A total of 870 Han Chinese subjects, including 435 PD patients and 435 healthy controls, were enrolled in this case-control study. Peripheral blood was obtained from all subjects for DNA extraction, and selected SNPs (rs730437, rs3752651, rs11506105) of the EGFR gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Differences in the frequencies of genotype and allele gene polymorphisms between patients with PD and healthy controls were analyzed using the Chi-square test. Logistic regression analysis was applied for calculating the odds ratios (ORs) and 95 % confidence intervals (CIs) to evaluate potential associations. RESULTS: We observed statistically significant differences in rs730437 in the additive models (AC vs. AA: P = 0.047), dominant models (CC + AC vs. AA: P = 0.024) and alleles (C vs. A: P = 0.018). Further subgroup analyses indicated that the C allele of rs730437 showed lower prevalence in the EOPD, compared with matched controls (P = 0.005). The frequency of the GG genotype and G allele for rs11506105 was lower in PD subjects than in healthy controls in the entire study population (P = 0.028, P = 0.034, respectively) and female group (P = 0.024, P = 0.007, respectively). No significant association was found between rs3752651 polymorphism and PD susceptibility in either the whole or subgroup analyses. The analysis of gene haplotypes revealed that the AAT haplotype was related with PD susceptibility. CONCLUSION: The rs730437 and rs11506105 polymorphisms, but not the rs3752651 polymorphism, of the EGFR gene may be related with susceptibility to PD in a Han Chinese population. An investigation using a larger sample size is warranted to further analyze potential associations between the EGFR gene and PD.

Laquinimod inhibits MMP+ induced NLRP3 inflammasome activation in human neuronal cells.

Objective: Nod-like receptor protein 3 (NLRP3) inflammasome plays anessentialrole in neuroinflammation in the Parkinson's disease (PD) progression. Laquinimodis an immunomodulator that is clinically used for the treatment of multiple sclerosis. This study aims to investigate whether laquinimod possessesa protective effect against MPP+-induced NLRP3 activation.Materials and methods: In a variety of tests on human SH-SY5Y neuronal cells, 1-methyl-4-phenyl Pyridine (MPP+) was used to mimic the microenvironment of PD. Activation of NLRP3 inflammasome was measured by western blot analysis and enzyme linked immunosorbent assay (ELISA).Results: Laquinimod had a significant protective impact against MPP+-induced neurotoxicity. Our results demonstrate that laquinimod prevented MPP+-induced reduction of cell proliferation, the release of lactate dehydrogenase (LDH), and apoptosis. Importantly, treatment with laquinimod significantly inhibited the activation of the NLRP3 inflammasome by reducing the levels of its components, including NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and cleaved caspase 1 (P10). Consistently, laquinimod prevented MPP+-induced secretions of interleukin 1ß (IL-1ß) and interleukin-18 (IL-18). Additionally, laquinimod also reduced the expression of other related factors, such as intracellular reactive oxygen species (ROS), NADPH oxidase 4 (NOX-4), thioredoxin-interacting protein (TxNIP). Furthermore, laquinimod prevented the reduction of sirtuin 1 (SIRT1) from MPP+ stimulation. Inhibition of SIRT1 abolished the protective effects of laquinimod against the activation of the NLRP3 inflammasome, suggesting the involvement of SIRT1 in this process.Conclusion: These findings suggest that laquinimod treatment might be a possible therapeutic strategy for neuroinflammation in PD.

Association of IL-16 gene polymorphisms with sporadic Parkinson's disease in a Han Chinese population.

This study was performed to investigate the genetic association of single-nucleotide polymorphisms (SNPs) in the interleukin-16 (IL-16) gene with the risk of Parkinson's disease (PD) in a Chinese Han population. Genotyping for the rs11556218 T/G, rs1131445 T/C and rs4072111 C/T polymorphisms of IL-16 was performed using the PCR-RFLP method in 405 patients with PD and 405 healthy matched individuals. Statistically significant difference for rs4072111 could be observed in both additive model (TC vs. CC: OR=0.622, 95 % CI: 0.443-0.873, P = 0.006) and dominant model (TC+TT vs. CC: OR =0.644, 95 % CI: 0.464-0.893, P = 0.008). The frequency of the rs4072111 T allele was significantly lower in the PD patients (OR= 0.692, 95 % CI: 0.515-0.929, P = 0.014) than in the controls. In subgroup analysis, a significant difference in genotype frequency distribution (P =0.004) and allele frequency (P =0.001) was found for rs4072111 between the male PD group and the control group, similar to the findings for the late-onset Parkinson's disease (LOPD) group and the control group (P = 0.044, 0.038, respectively). Conversely, there was no significant difference in the frequencies of rs11556218 and rs1131445 between the PD patients and controls. Moreover, seven common haplotypes were detected, and the CGT and CTC haplotypes were associated with PD susceptibility in our study. Our results indicate that the IL-16 gene rs4072111 polymorphism is significantly associated with PD susceptibility in the Chinese Han population but that the polymorphisms rs11556218 and rs4778889 are not.