α‐Synuclein induces apoptosis by altered expression in human peripheral lymphocytes in Parkinson’s disease

Kim, Seonghan; Jeon, Beom S.; Heo, Chaejeong; Im, Pil Seon; Ahn, Tae-Beom; Seo, Jeong-Sun; Kim, Hye‐Sun; Park, Cheol Hyoung; Choi, Se Hoon; Cho, Seo-Hyun; Lee, Wang Jae; Suh, Yoo‐Hun

doi:10.1096/fj.04-1917fje

Cited by 80 publications

(53 citation statements)

References 66 publications

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“…In contrast to brain neuronal cells, human PBMCs represent a valuable source in the study of PD-related proteins due to their easy accessibility [30,31,32]. Our analysis of these cells demonstrated an apparently higher protein expression of CCDC62 in patients carrying the AA genotype.…”

Section: Discussionmentioning

confidence: 94%

CCDC62 Variant rs12817488 Is Associated with the Risk of Parkinson's Disease in a Han Chinese Population

Liu¹,

Zhou²,

Cheng³

et al. 2013

Eur Neurol

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It has been recently proposed by a genome-wide association study (GWAS) meta-analysis that the CCDC62 variant rs12817488 is a new risk locus associated with Parkinson's disease (PD). In this study, we aimed to investigate the association between rs12817488 and PD in a Chinese cohort. A total of 341 PD patients and 423 matched controls were recruited in Eastern China. Our results showed that the A allele of rs12817488 was significantly associated with an aggravated risk of PD (p = 0.006) and represented a major allele in contrast to a minor one in Caucasians. Genotype distributions also differed between PD patients and controls (p = 0.011 for AA/AG/GG). Further analysis showed that the association of rs12817488 with PD only existed in females. We also investigated the protein level of CCDC62 in peripheral blood mononuclear cells from 41 AA or GG carriers and found an apparently higher expression in PD patients carrying the AA genotype. A potential interaction was found between two estrogen-related loci, i.e. rs12817488/CCDC62 and rs2697962/PRDM2, particularly in the female stratum. In conclusion, our study demonstrated for the first time a significant association between the rs12817488 polymorphism and PD predisposition in a Chinese population with gender variations and provides new insight regarding the variant's protein expression and estrogen-related genetic interaction.

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Section: Discussionmentioning

confidence: 94%

CCDC62 Variant rs12817488 Is Associated with the Risk of Parkinson's Disease in a Han Chinese Population

Liu¹,

Zhou²,

Cheng³

et al. 2013

Eur Neurol

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“…The protein has been previously found in the two main components of blood, plasma and RBCs, and cerebrospinal fluid [24][25][26][27]. In the present study, we first quantified the oligomeric forms of a-synuclein in the human RBCs in the ischemic stroke patients and compared with that in PD patients and healthy people.…”

Section: Discussionmentioning

confidence: 96%

A comparative study of the amount of α-synuclein in ischemic stroke and Parkinson’s disease

Zhao

Wang

et al. 2016

Neurol Sci

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In the present study, we detected the level of oligomeric form of α-synuclein in the red blood cells of ischemic stroke, Parkinson's disease, and normal people and compared the differences to assess the diagnosis potential of α-synuclein in ischemic stroke patients. 86 ischemic stroke, 100 PD, and 102 healthy cases were enrolled in the present study. Total protein amount in the red blood cells were quantified by BCA assay using spectrophotometer. Levels of oligomeric form of α-synuclein were characterized by a sandwich ELISA. Analysis of correlation analysis and receiver operating characteristic curve were conducted. Significant differences were detected in the levels of oligomeric forms of α-synuclein in different samples' blood cells (P < 0.05); the levels of total protein in (188.1 ± 33.9 mmol/L) healthy people were significantly higher than that of PD (147.7 ± 45.0 mmol/L) and ischemic stroke groups (142.9 ± 43.0 mmol/L) (P < 0.05). There was no correlation between the age of patients and level of α-synuclein (R (2) = 0.216 in ischemic stroke group and -0.104 in PD group) and the receiver operating characteristic curve analysis showed a high sensitivity of α-synuclein in discriminating ischemic stroke (sensitivity was 63.7 % and specificity was 9.6 %) and PD (sensitivity was 44.1 % and specificity was 12.5 %) patients from the controls. The levels of oligomeric form of α-synuclein of red blood cells in ischemic stroke and Parkinson's disease patients were both significant higher than normal people. And the level of oligomeric form α-synuclein showed a potential for diagnosis of ischemic stroke in clinic.

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“…In this work, we have studied SNCA expression in the hematopoietic system of a PD patient, as this gene is known to be expressed in several hematopoietic lineages in adults, such as lymphocytes [Kim et al, 2004], platelets [Li et al, 2002], and erythroid lineage [Nakai et al, 2007].…”

Section: Discussionmentioning

confidence: 99%

Allelic imbalance of expression and epigenetic regulation within the alpha-synuclein wild-type and p.Ala53Thr alleles in Parkinson disease

et al. 2010

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Genetic alterations in the alpha-synuclein (SNCA) gene have been implicated in Parkinson Disease (PD), including point mutations, gene multiplications, and sequence variations within the promoter. Such alterations may be involved in pathology through structural changes or overexpression of the protein leading to protein aggregation, as well as through impaired gene expression. It is, therefore, of importance to specify the parameters that regulate SNCA expression in its normal and mutated state. We studied the expression of SNCA alleles in a lymphoblastoid cell line and in the blood cells of a patient heterozygous for p.Ala53Thr, the first mutation to be implicated in PD pathogenesis. Here, we provide evidence that: (1) SNCA shows monoallelic expression in this patient, (2) epigenetic silencing of the mutated allele involves histone modifications but not DNA methylation, and (3) steady-state mRNA levels deriving from the normal SNCA allele in this patient exceed those of the two normal SNCA alleles combined, in matching, control individuals. An imbalanced SNCA expression in this patient is thus documented, with silencing of the p.Ala53Thr allele and upregulation of the wild-type-allele. This phenomenon is demonstrated for a first time in the SNCA gene, and may have important implications for PD pathogenesis.

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α‐Synuclein induces apoptosis by altered expression in human peripheral lymphocytes in Parkinson’s disease

Cited by 80 publications

References 66 publications

<b><i>CCDC62</i></b> Variant rs12817488 Is Associated with the Risk of Parkinson's Disease in a Han Chinese Population

<b><i>CCDC62</i></b> Variant rs12817488 Is Associated with the Risk of Parkinson's Disease in a Han Chinese Population

A comparative study of the amount of α-synuclein in ischemic stroke and Parkinson’s disease

Allelic imbalance of expression and epigenetic regulation within the alpha-synuclein wild-type and p.Ala53Thr alleles in Parkinson disease

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