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GBA1 is one of the common risk genes of Parkinson′s disease (PD), which encodes glucocerebrosidase. It is difficult to distinguish PD patients with heterozygous variants of GBA1 ( GBA1-PD) from idiopathic Parkinson′s disease patients, but GBA1-PD tends to progress faster, be more severe, and be more likely to be associated with cognitive impairment and other non-motor symptoms. The pathological mechanism of the increased risk of PD in GBA1 heterozygous variant carriers may be related to autophagy-lysosome dysfunction and mitochondrial dysfunction. Targeted therapy for GBA1 is expected to become a new direction of precision therapy for PD. In this article, the epidemiology and clinical features of GBA1-PD, the possible pathogenesis of GBA1 variation, and the therapeutic strategies for GBA1-PD were elaborated.
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Objective:To investigate the characteristics and associated factors of depression in elderly patients with Parkinson's disease(PD).Methods:A total of 1138 elderly PD patients from Xuanwu Hospital of Capital Medical University were consecutively enrolled.The Hamilton Depression 17-item Scale(HAMD-17)was used to diagnose depression(scores ≥14). The depressive characteristics of PD patients with depression and those without depression were compared, and Logistic regression model was used to analyze the clinical risk factors of depression in PD patients.Results:Among the 1 138 PD patients, 233 cases had depression.The incidence of depression in PD patients was 20.5%, and the treatment rate was only 6.0%(14 cases). The main symptoms of depression in PD patients included sleep disturbance(101 cases, 43.3%), depression(57 cases, 24.5%), work and interest loss(49 cases, 21%). Compared to PD patients without depression, PD patients with depression were more likely women(49.4% vs36.3%), and had lower cognitive scores[(25.56 ± 4.22)scores vs(27.07 ± 3.08)scores], higher rate of freezing of gait(51.0% vs24.0%), higher incidence of disability(87.1% vs28.5%)( P<0.05). A comparison of each part of the unified Parkinson's disease rating scale(UPDRS)between the two groups revealed that the scores of activities of daily living[(16.52 ± 8.71)scores vs(10.15 ± 5.48)scores], the motor examination[(33.78 ± 19.48)scores vs(22.87 ±13.08)scores]and the complications of therapy[2.0(0.0, 6.0)scores vs0.0(0.0, 2.0)scores]were higher in the PD patients with depression group than in the PD patients without depression group( P<0.05). Logistic regression analysis showed that women( OR=1.532, 95% CI: 1.073-2.187, P=0.019), disability( OR=6.357, 95% CI: 4.399-9.186, P<0.001), activities of daily living evaluated by UPDRS( OR=1.093, 95% CI: 1.043-1.146, P<0.001)and motor complications( OR=1.100, 95% CI: 1.014-1.193, P=0.022)were independent risk factors for PD depression. Conclusions:Depression was common in PD patients and usually manifested as sleep disturbance and low motivation, women, motor complications, disability and decreased quality of daily living were independent risk factors for depression.
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ObjectiveTo investigate the relationship between polymorphism in the PITX3 gene and hereditary susceptibility of Parkinson's disease (PD). MethodsThree PITX3 single nucleotide polymorphisms ( SNPs ),including rs2281983,rs4919621 and rs3758549 were examined in 509 late-onset PD patients ( LOPD ),290 early-onset PD(EOPD) and 494 healthy controls.Genotyping was carried out in all subjects using a ligase detection reaction( LDR).ResultsAllele and genotype frequencies did not differ between the 799 PD patients and 494 controls ( P values of genotype were 0.494,0.343,0.951 ; P values of allele were 0.369,0.297,0.823 ),between 509 LOPD patients and 494 controls ( P values of genotype were 0.522,0.350,0.630 ; P values of allele were 0.413,0.328,0.571 ),between 290 EOPD patients and 494 controls ( P values of genotype were 0.499,0.492,0.552; P values of allele were 0.321,0.301,0.931 ),and between 509 LOPD and 290 EOPD patients ( P values of genotype were 0.577,0.710,0.127 ; P values of allele were 0.346,0.472,0.077 ) for all three SNPs (rs2281983,rs4919621 and rs3758549).There were no association petween the three PITX3 SNPs and PD.ConclusionThree PITX3 SNPs do not contribute to the risk of developing PD in Chinese population.
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Objective To observe the relation between onset age and the motor complications involved Parkinaon' s disease (PD).Methods The detailed clinical information of 195 patients with idiopathic PD and good response to L-dopa were recorded and followed up.The data were calculated with SPSS statistic software.Results Although the time interval between the onset of the disease and the use of L-dopa was significantly longer in the 57 early-onset patients as compared to the 138 later-onset ones ((3.88±3.33) years vs (2.36±2.21) years, t = 3.142, P = 0.002), the time interval between the use of L-dopa and the occurrence of motor complications was not significantly longer in the early-onset group ((3.81±2.06) years vs (4.24±2.00) years, t = -0.888, P = 0.378).There was no difference in the constituent ratio of non-L-dopa use from onset between early-onset and later-onset PD groups (28.07% (16/57) vs 27.54% (38/138), χ2 = 0.006, P = 0.940).There was also no difference in the dosage of daily L-dopa use when motor complications occurred between early-onset and later-onset PD groups ((601.8± 296.7) mgvs (655.6±192.5) mg, t = -0.912, P=0.365).Seven-tenths of the patients with an onset age younger than 40 years old carried the risk of motor complications after using L-dopa for 5-years and those older than 70 years had the risk at a rate of 1/10.Conclusions Delaying the of use of L-dopa may not necessarily delay the onset of motor complications.The high incidence of motor complications among younger patients may not be related with drug dosage and the type of drug firstly chosen.Younger onset age does inerease the ineidence of motor complicatious.
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BACKGROUND: The transplantation of microencapsulated cell is becoming a hotspot modality in the therapy of Parkinson disease (PD). The application of Alginate-polysysine-alginate (APA) is currently limited due to fragility and pericystic fibrosis although it has been used in clinic. In this study, the native Alginate-chitosan-alginate(ACA)microencapsulated pheochromocytoma cells (PC12 cells) are transplanted into the region of corpus striatum in the injured side of the brain of the PD rat model, the functional recovery of rotational behavior and pathological changes are also observed in the control, sham and treated groups.OBJECTIVE: To observe whether the transplantation of ACA microencapsulated PC12 cells into the brain can improve the rotational behavior in the rat model of PD.DESIGN: Randomized controlled experiment.SETTING: Dalian Research Institute of Physiochemistry, Chinese Academy of Sciences.MATERIALS: Totally 40 adult male Wistar rats with body mass of(220±10) g, ACA microcapsule and PC12 cells were used in this study.METHODS: The experiment was carried out in the animal experimental laboratory of Second Hospital, Jilin University and Dalian Research Institute of Physicochemistry, Chinese Academy of Sciences between May and December 2002. Native ACA were used to microencapsulate the PC12cells. These rats were randomly divided into the following three groups,treated group (10 rats received microencapsulated PC12 cell transplantation), control group (7 rats received unencapsulated PC12 cell transplantation) and sham group (6 rats received empty microencapsule transplantation). The transplantation site was the region of corpus striatum in the injured side of brain. The difference of rotational behavior included by apomorphine was compared before and after the transplantation in these rats,the morphological changes of the transplanted microcapsules and activity of the microencapsulated cells were also detected.MAIN OUTCOME MEASURES: ①Rotational behavior of the rats before and after transplantation. ②Pathological change in the regions of substantia nigra and corpus striatum. ③ The integrality of retrieved microencapsule and the bioactivity of retrieved PC12 cells.RESULTS: ① At the 4th week of transplantation, rotational behavior was significantly decreased in the encapsulated PC12 cells treated group compared with that of the groups received empty microencapsules transplantation [(6.9±2.8),(10.5±1.6) r/min, P ＜ 0.05].Tbis behavioral improvement could last at least three months. Although the unencapsulated PC12 cells also can improve the rotational behavior compared with before transplantation[(5.6±l.1 ), (9.5±1.5) r/min, P ＜ 0.05], which only lasted two months and fetal tumor formed in the skull of some rats. There was no significant difference in rotational behavior of the rats before and after transplantation in the empty microencapsule transplantation group. PC12 cells of retrieved microencapsulate grew well after re-culture, and have bioactivity.CONCLUSION: Transplantation of ACA microencapsulated PC12 cells into the brain can improve can improve the rotational behavior of rat PD model induced by apomorphine. ACA microcapsule can both isolate the host's immune system effectively and prevent the formation of tumor, and have a promising application in clinic.