<sup>99m</sup>Tc‐TRODAT‐1 SPECT Showing Dopaminergic Deficiency in a Patient with Spinocerebellar Ataxia Type 10 and Parkinsonism

Fabiani, G; Martins, Raul; Ashizawa, Tetsuo; Germiniani, Francisco Manoel Branco; Teive, Hélio Afonso Ghizoni

doi:10.1002/mdc3.12700

Cited by 3 publications

(3 citation statements)

References 4 publications

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“…In this study, gene sets for neurodegenerative disorders were either curated manually using the OMIM database and published literature or were derived from the results of GWAS meta-analyses. Interestingly, among the three hereditary progressive ataxia genes that overlapped with our meta-DEG gene set, mutations in ATXN10 were reported to present with levodopa-responsive parkinsonism, or reduction of dopamine transporter binding, as documented by 99mTc-TRODAT-1 SPECT (Schüle et al, 2017;Fabiani et al, 2019), although these findings were not included in the OMIM database. Subgroup analyses after dividing DEGs into up-and downregulated genes was only possible in the current study.…”

Section: Discussionmentioning

confidence: 99%

Meta-Analysis of Differentially Expressed Genes in the Substantia Nigra in Parkinson’s Disease Supports Phenotype-Specific Transcriptome Changes

et al. 2020

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BackgroundStudies regarding differentially expressed genes (DEGs) in Parkinson’s disease (PD) have focused on common upstream regulators or dysregulated pathways or ontologies; however, the relationships between DEGs and disease-related or cell type-enriched genes have not been systematically studied. Meta-analysis of DEGs (meta-DEGs) are expected to overcome the limitations, such as replication failure and small sample size of previous studies.PurposeMeta-DEGs were performed to investigate dysregulated genes enriched with neurodegenerative disorder causative or risk genes in a phenotype-specific manner.MethodsSix microarray datasets from PD patients and controls, for which substantia nigra sample transcriptome data were available, were downloaded from the NINDS data repository. Meta-DEGs were performed using two methods, combining p-values and combing effect size, and common DEGs were used for secondary analyses. Gene sets of cell type-enriched or disease-related genes for PD, Alzheimer’s disease (AD), and hereditary progressive ataxia were constructed by curation of public databases and/or published literatures.ResultsOur meta-analyses revealed 449 downregulated and 137 upregulated genes. Overrepresentation analyses with cell type-enriched genes were significant in neuron-enriched genes but not in astrocyte- or microglia-enriched genes. Meta-DEGs were significantly enriched in causative genes for hereditary disorders accompanying parkinsonism but not in genes associated with AD or hereditary progressive ataxia. Enrichment of PD-related genes was highly significant in downregulated DEGs but insignificant in upregulated genes.ConclusionDownregulated meta-DEGs were associated with PD-related genes, but not with other neurodegenerative disorder genes. These results highlight disease phenotype-specific changes in dysregulated genes in PD.

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Section: Discussionmentioning

confidence: 99%

Meta-Analysis of Differentially Expressed Genes in the Substantia Nigra in Parkinson’s Disease Supports Phenotype-Specific Transcriptome Changes

et al. 2020

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“…ATXN10 mutations present with levodopa-responsive parkinsonism with presynaptic loss of dopamine, as documented with 99m Tc-TRODAT-1 SPECT. 12 The final gene set consisted of 19 PARK genes and 77 non- PARK genes. Genes with more than two OMIM phenotype IDs, such as assignment of PARK loci and hereditary atypical parkinsonian disorders (e.g., ATP13A2 and PLA2G6 ), were categorized as PARK genes.…”

Section: Methodsmentioning

confidence: 99%

“…Next, the PPI annotations underwent quality control and filtering, as previously described. 8 12 Briefly, all non-human TaxID annotations, all annotations with non-assigned interaction detection methods or PubMed identifiers, all annotations with generic specifications, and all proteins whose transcripts were not expressed in the brain ( https://www.proteinatlas.org/humanproteome/brain/human+brain ) were removed. Then, a threshold was determined, and the filtered interactions were scored by evaluating the number of publications and detection methods reporting an interaction.…”

Section: Methodsmentioning

confidence: 99%

The Protein-Protein Interaction Network of Hereditary Parkinsonism Genes Is a Hierarchical Scale-Free Network

Kim

Lee

et al. 2022

Yonsei Med J

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Purpose Hereditary parkinsonism genes consist of causative genes of familial Parkinson’s disease (PD) with a locus symbol prefix ( PARK genes) and hereditary atypical parkinsonian disorders that present atypical features and limited responsiveness to levodopa (non- PARK genes). Although studies have shown that hereditary parkinsonism genes are related to idiopathic PD at the phenotypic, gene expression, and genomic levels, no study has systematically investigated connectivity among the proteins encoded by these genes at the protein-protein interaction (PPI) level. Materials and Methods Topological measurements and physical interaction enrichment were performed to assess PPI networks constructed using some or all the proteins encoded by hereditary parkinsonism genes (n=96), which were curated using the Online Mendelian Inheritance in Man database and literature. Results Non- PARK and PARK genes were involved in common functional modules related to autophagy, mitochondrial or lysosomal organization, catecholamine metabolic process, chemical synapse transmission, response to oxidative stress, neuronal apoptosis, regulation of cellular protein catabolic process, and vesicle-mediated transport in synapse. The hereditary parkinsonism proteins formed a single large network comprising 51 nodes, 83 edges, and three PPI pairs. The probability of degree distribution followed a power-law scaling behavior, with a degree exponent of 1.24 and a correlation coefficient of 0.92. LRRK2 was identified as a hub gene with the highest degree of betweenness centrality; its physical interaction enrichment score was 1.28, which was highly significant. Conclusion Both PARK and non- PARK genes show high connectivity at the PPI and biological functional levels.

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^99mTc‐TRODAT‐1 SPECT Showing Dopaminergic Deficiency in a Patient with Spinocerebellar Ataxia Type 10 and Parkinsonism

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Cited by 3 publications

References 4 publications

Meta-Analysis of Differentially Expressed Genes in the Substantia Nigra in Parkinson’s Disease Supports Phenotype-Specific Transcriptome Changes

Meta-Analysis of Differentially Expressed Genes in the Substantia Nigra in Parkinson’s Disease Supports Phenotype-Specific Transcriptome Changes

The Protein-Protein Interaction Network of Hereditary Parkinsonism Genes Is a Hierarchical Scale-Free Network

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