The metabolomics of alpha-synuclein (SNCA) gene deletion and mutation in mouse brain

Metabolomics ◽  
2013 ◽  
Vol 10 (1) ◽  
pp. 114-122 ◽  
Author(s):  
Ruth E. Musgrove ◽  
James Horne ◽  
Richard Wilson ◽  
Anna E. King ◽  
Lindsay M. Edwards ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Gene Deletion ◽  
Alpha Synuclein ◽  
Snca Gene

Conditional control of human wild-type and Parkinson's disease-associated mutant alpha-synuclein in transgenic mouse brain

2004 ◽  
Vol 31 (S 1) ◽  
Author(s):  
S Nuber ◽  
T Schmidt ◽  
D Berg ◽  
M Neumann ◽  
C Holzmann ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transgenic Mouse ◽  
Mouse Brain ◽  
Alpha Synuclein ◽  
Wild Type ◽  
Conditional Control ◽  
Human Wild Type

‘Seeding’ Alpha-Synuclein Spreads Parkinsonʼs Pathology in Normal Mouse Brain

2013 ◽  
Vol 13 (4) ◽  
pp. 5-6
Author(s):  
Richard Robinson
Keyword(s):  
Mouse Brain ◽  
Normal Mouse ◽  
Alpha Synuclein ◽  
Normal Mouse Brain

scholarly journals The SNCA-Rep1 Polymorphic Locus: Association with the Risk of Parkinson’s Disease and SNCA Gene Methylation

Acta Naturae ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 105-110 ◽  
Author(s):  
E. V. Iakovenko ◽  
N. Yu. Abramycheva ◽  
E. Yu. Fedotova ◽  
S. N. Illarioshkin
Keyword(s):  
Molecular Marker ◽  
Polymorphic Locus ◽  
Alpha Synuclein ◽  
Gene Methylation ◽  
Allelic Variants ◽  
Parkinsons Disease ◽  
Cpg Sites ◽  
Snca Gene ◽  
Intron 1 ◽  
Significant Region

Neurodegeneration in Parkinsons disease is characterized by the accumulation of alpha-synuclein, aprotein encoded by theSNCAgene, in neurons. In addition to mutations, many polymorphisms have been identified in this gene, and one of theseis a dinucleotide microsatellite:SNCA-Rep1.The mechanisms by which specific configurations ofSNCA-Rep1 may contribute to the development of this disease have yet to be clarified. Inour study, a relationship between longSNCA-Rep1 alleles and Parkinsons was confirmed in the Russian population. Long allelic variants ofSNCA-Rep1 were shown to be associated with the hypomethylation of the CpG-sites in intron 1 of theSNCAgene. Long variants ofSNCA-Rep1 are supposed to exert their effect through the hypomethylation of atranscriptionally significant region of this gene. Hypomethylation is usually associated with increased expression, which, in turn, contributes to alpha-synuclein accumulation in neuronal cytoplasm, with the latter being the main molecular marker of Parkinsons disease. Further studies are needed to establish a relationship between our finding andSNCAgene expression.

scholarly journals In vivo phenotyping of Parkinson-specific stem cells reveals increased a-Synuclein levels but no spreading

2017 ◽  
Author(s):  
Kathrin Hemmer ◽  
Lisa M. Smits ◽  
Silvia Bolognin ◽  
Jens C. Schwamborn
Keyword(s):  
Parkinson’S Disease ◽  
Stem Cells ◽  
Parkinson's Disease ◽  
Mouse Brain ◽  
Disease Modeling ◽  
Disease Patient ◽  
Alpha Synuclein ◽  
Patient Specific ◽  
Species Barrier

AbstractParkinson′s disease is a progressive age-associated neurological disorder. One of the major neuropathological hallmarks of Parkinson’s disease is the appearance of protein aggregates, mainly consisting of the protein alpha-Synuclein. These aggregates have been described both in genetic as well as idiopathic forms of the disease. Currently, Parkinson’s disease patient-specific induced pluripotent stem cells (iPSCs) are mainly used for in vitro disease modeling or for experimental cell replacement approaches. Here, we demonstrate that these cells can be used for in vivo disease modeling. We show that Parkinson’s disease patient-specific, iPSC-derived neurons carrying the LRRK2-G2019S mutation show an upregulation of alpha-Synuclein after transplantation in the mouse brain. However, further investigations indicate that the increased human alpha-Synuclein levels fail to induce spreading or aggregation in the mouse brain. We therefore conclude that grafting of these cells into the mouse brain is suitable for cell autonomous in vivo disease modeling but has strong limitations beyond that. Furthermore, our results support the hypothesis that there might be a species barrier between human to mouse concerning alpha-Synuclein spreading.

scholarly journals A single nucleotide polymorphism in the 3′UTR of the SNCA gene encoding alpha-synuclein is a new potential susceptibility locus for Parkinson disease

2009 ◽  
Vol 461 (2) ◽  
pp. 196-201 ◽  
Author(s):  
Sotiria Sotiriou ◽  
Gretchen Gibney ◽  
Andreas D. Baxevanis ◽  
Robert L. Nussbaum
Keyword(s):  
Single Nucleotide Polymorphism ◽  
Parkinson Disease ◽  
Alpha Synuclein ◽  
Susceptibility Locus ◽  
Nucleotide Polymorphism ◽  
Gene Encoding ◽  
Single Nucleotide ◽  
Snca Gene

scholarly journals TNF gene deletion prevents lipopolysaccharide-mediated sensitisation of the neonatal mouse brain to hypoxic-ischaemic insult

2012 ◽  
Vol 6 (S4) ◽  
Author(s):  
A Sahota ◽  
G Kendall ◽  
S Lange ◽  
G Raivich
Keyword(s):  
Mouse Brain ◽  
Gene Deletion ◽  
Neonatal Mouse ◽  
Tnf Gene ◽  
Ischaemic Insult

scholarly journals The landscape of SNCA transcripts across synucleinopathies: New insights from long reads sequencing analysis

2019 ◽  
Author(s):  
Elizabeth Tseng ◽  
William J Rowell ◽  
Omolara-Chinue Glenn ◽  
Ting Hon ◽  
Julio Barrera ◽  
...  
Keyword(s):  
Disease Risk ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Sequencing Analysis ◽  
Snca Gene ◽  
Long Reads ◽  
Long Read ◽  
Alternatively Spliced ◽  
Gene Transcripts ◽  
And Control

AbstractDysregulation of alpha-synuclein expression has been implicated in the pathogenesis of synucleinopathies, in particular Parkinson’s Disease (PD) and Dementia with Lewy bodies (DLB). Previous studies have shown that the alternatively spliced isoforms of the SNCA gene are differentially expressed in different parts of the brain for PD and DLB patients. Similarly, SNCA isoforms with skipped exons can have a functional impact on the protein domains. The large intronic region of the SNCA gene was also shown to harbor structural variants that affect transcriptional levels. Here we apply the first study of using long read sequencing with targeted capture of both the gDNA and cDNA of the SNCA gene in brain tissues of PD, DLB, and control samples using the PacBio Sequel system. The targeted full-length cDNA (Iso-Seq) data confirmed complex usage of known alternative start sites and variable 3’ UTR lengths, as well as novel 5’ starts and 3’ ends not previously described. The targeted gDNA data allowed phasing of up to 81% of the ~114kb SNCA region, with the longest phased block excedding 54 kb. We demonstrate that long gDNA and cDNA reads have the potential to reveal long-range information not previously accessible using traditional sequencing methods. This approach has a potential impact in studying disease risk genes such as SNCA, providing new insights into the genetic etiologies, including perturbations to the landscape the gene transcripts, of human complex diseases such as synucleinopathies.

Epigenetic regulation of SNCA gene expression in Parkinson’s disease

2020 ◽  
pp. 96-98
Author(s):  
А.К. Емельянов ◽  
А.О. Лавринова ◽  
Н.В. Мельникова ◽  
А.А. Дмитриев ◽  
И.В. Милюхина ◽  
...  
Keyword(s):  
Gene Expression ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Cpg Island ◽  
Alpha Synuclein ◽  
Peripheral Blood Cells ◽  
Snca Gene ◽  
Intron 1 ◽  
And Control ◽  
First Time

В настоящем исследовании проведена оценка уровня мРНК и белка генов SNCA, DNMT1, а также степени метилирования интрона 1 гена SNCA в CD45+ клетках периферической крови пациентов со спорадической болезнью Паркинсона (БП) и индивидуумов контрольной группы. Впервые было выявлено снижение концентрации белка DNMT1 в CD45+ клетках периферической крови пациентов с БП по сравнению с группой контроля. Обнаружено увеличение уровня мРНК гена DNMT1 у пациентов с БП по сравнению с контролем. Не выявлено статистически значимых различий при сравнении степени метилирования интрона 1 гена SNCA в CD45+ клетках периферической крови пациентов с БП и контроля. В группе контроля выявлена обратная корреляция степени метилирования отдельных CpG островков с концентрацией белка альфа-синуклеина и уровнем мРНК гена SNCA. Проведенное исследование позволяет предположить участие гена DNMT1 в патогенезе БП и отсутствие ассоциации степени метилирования интрона 1 гена SNCA с БП. The aim of this study was to assess the level of mRNA and protein of the SNCA, DNMT1 genes, as well as intron 1 methylation of the SNCA gene in CD45 + peripheral blood cells of patients with sporadic PD and control individuals. For the first time, a decrease in the concentration of DNMT1 protein in CD45 + peripheral blood cells from PD patients compare to controls was revealed. An increase in DNMT1 gene expression in PD patients compare to controls was found. No differences in intron 1 methylation of the SNCA gene in CD45 + peripheral blood cells was found between PD patients and controls. An inverse correlations between methylation level of 21, 22 CpG island in intron1 of SNCA gene and mRNA SNCA gene and alpha-synuclein protein level were found. The study suggests the involvement of DNMT1 in the pathogenesis of PD and the lack of association of PD with intron 1 methylation of the SNCA gene.

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