Intermediate-length CAG repeat in ATXN2 is associated with increased risk for amyotrophic lateral sclerosis in Brazilian patients

Andrade, Helen Maia Tavares de; Cintra, Vívian Pedigone; Albuquerque, Milena de; Piccinin, Camila; Bonadia, Luciana Cardoso; Couteiro, Rafael Esteves Duarte; Oliveira, Daniel Sabino de; Claudino, Rinaldo; Gonçalves, Marcos Vinicius Magno; Dourado, Mário Emílio; Souza, Leonardo Cruz de; Teixeira, Antônio Lúcio; Prado, Laura de Godoy Rousseff; Tumas, Vítor; Oliveira, Acary Souza Bullé; Nucci, Anamarli; Lopes-Cendes, Íscia; Marques, Wilson; França, Marcondes C.

doi:10.1016/j.neurobiolaging.2018.04.020

Cited by 16 publications

(4 citation statements)

References 27 publications

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“…21 Intermediate CAG expansions at ATXN2 have been associated with ALS in multiple populations. 22 In contrast to other previously mentioned genes, this is not a causative gene, but rather a risk gene. On the other hand, its frequency is much higher in the overall ALS public compared to the other monogenic ALS subtypes.…”

Section: Sod1-alsmentioning

confidence: 81%

Gene-based therapies for neuromuscular disorders

Zanoteli,

França,

Marques

2024

Arq Neuropsiquiatr

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Neuromuscular diseases (NMD) include a broad group of medical conditions with both acquired and genetic causes. In recent years, important advances have been made in the treatment of genetically caused NMD, and most of these advances are due to the implementation of therapies aimed at gene regulation. Among these therapies, gene replacement, small interfering RNA (siRNA), and antisense antinucleotides are the most promising approaches. More importantly, some of these therapies have already gained regulatory approval or are in the final stages of approval. The review focuses on motor neuron diseases, neuropathies, and Duchenne muscular dystrophy, summarizing the most recent developments in gene-based therapies for these conditions.

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Section: Sod1-alsmentioning

confidence: 81%

Gene-based therapies for neuromuscular disorders

Zanoteli,

França,

Marques

2024

Arq Neuropsiquiatr

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“…Combined with the results of the above miRNA-circRNA interactions, there were only five DEcircRNAs meeting the above three simultaneous requirements (backsplice reads of any sample were not zero, exons ≥3, and had a miRNA-circRNA interaction). The Venn Among the above five DEcircRNAs, circ-ATXN2 (circRNA-1783), which originates from the 20 exons of ATXN2 genes, has been reported to be involved in aging-related diseases, such as amyotrophic lateral sclerosis (Liu et al, 2013;Lu et al, 2015;Tavares de Andrade et al, 2018;Zhao et al, 2018;Watanabe et al, 2020;Laffita-Mesa et al, 2021), metabolism (Carmo-Silva et al, 2017), T2D, CAD, blood pressure, and inflammation (Odegaard and Chawla 2013;Kraja et al, 2014;Carmo-Silva et al, 2017), and is associated with parental longevity and longevity (Franceschi et al, 2020). On a fat-enriched diet, ataxin-2-deficient animals showed increased weight gain (Kiehl et al, 2006).…”

Section: Characterization Of Circ-atxn2 In Rat Satmentioning

confidence: 99%

A Novel Age-Related Circular RNA Circ-ATXN2 Inhibits Proliferation, Promotes Cell Death and Adipogenesis in Rat Adipose Tissue-Derived Stromal Cells

Song

Xing

et al. 2021

Front. Genet.

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Adipose tissue-derived stromal cells are promising candidates investigating the stem cell-related treatment. However, their proportion and utility in the human body decline with time, rendering stem cells incompetent to complete repair processes in vivo. The involvement of circRNAs in the aging process is poorly understood. Rat subcutaneous adipose tissue from 10-week-old and 27-month-old rats were used for hematoxylin and eosin (H and E) staining, TUNEL staining, and circRNA sequencing. Rat adipose tissue-derived stromal cells were cultured and overexpressed with circ-ATXN2. Proliferation was examined using xCELLigence real-time cell analysis, EdU staining, and cell cycle assay. Apoptosis was induced by CoCl2 and examined using flow cytometry. RT-PCR assay and Oil Red O staining were used to measure adipogenesis at 48 h and 14 days, respectively. H and E staining showed that the diameter of adipocytes increased; however, the number of cells decreased in old rats. TUNEL staining showed that the proportion of apoptotic cells was increased in old rats. A total of 4,860 and 4,952 circRNAs was detected in young and old rats, respectively. Among them, 67 circRNAs exhibited divergent expression between the two groups (fold change ≥2, p ≤ 0.05), of which 33 were upregulated (49.3%) and 34 were downregulated (50.7%). The proliferation of circ-ATXN2-overexpressing cells decreased significantly in vitro, which was further validated by xCELLigence real-time cell analysis, EdU staining, and cell cycle assay. Overexpression of circ-ATXN2 significantly increased the total apoptotic rate from 5.78 ± 0.46% to 11.97 ± 1.61%, early apoptotic rate from 1.76 ± 0.22% to 5.50 ± 0.66%, and late apoptosis rate from 4.02 ± 0.25% to 6.47 ± 1.06% in adipose tissue-derived stromal cells. Furthermore, in circ-ATXN2-overexpressing cells, RT-PCR assay revealed that the expression levels of adipose differentiation-related genes PPARγ and CEBP/α were increased and the Oil Red O staining assay showed more lipid droplets. Our study revealed the expression profile of circRNAs in the adipose tissue of old rats. We found a novel age-related circular RNA—circ-ATXN2—that inhibits proliferation and promotes cell death and adipogenesis in rat adipose tissue-derived stromal cells.

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“…Interestingly, patients from India also showed similar data to Europeans, as 4.6% (6/131 patients) of the investigated ALS patients carried an intermediate length allele (between 27 and 32 repeats) of the ATXN2 gene [ 47 ]. The highest percentage of ALS patients carrying the intermediate repeat expansion has been reported from Brazil, where 6.3% (29/459 patients) of ALS patients were tested positive for ATXN2 intermediate alleles [ 48 ]. Reports from China found a significantly lower rate of ATXN2 intermediate alleles (1.6, 1.5 and 1.9%) among ALS patients as studies involving patients of European origin [ 49 – 51 ].…”

Section: Introductionmentioning

confidence: 99%

Beyond C9orf72: repeat expansions and copy number variations as risk factors of amyotrophic lateral sclerosis across various populations

Nagy,

Pál,

Engelhardt

et al. 2024

BMC Med Genomics

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder which is characterized by the loss of both upper and lower motor neurons in the central nervous system. In a significant fraction of ALS cases - irrespective of family history- a genetic background may be identified. The genetic background of ALS shows a high variability from one ethnicity to another. The most frequent genetic cause of ALS is the repeat expansion of the C9orf72 gene. With the emergence of next-generation sequencing techniques and copy number alteration calling tools the focus in ALS genetics has shifted from disease causing genes and mutations towards genetic susceptibility and risk factors.In this review we aimed to summarize the most widely recognized and studied ALS linked repeat expansions and copy number variations other than the hexanucleotide repeat expansion in the C9orf72 gene. We compare and contrast their involvement and phenotype modifying roles in ALS among different populations.

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Intermediate-length CAG repeat in ATXN2 is associated with increased risk for amyotrophic lateral sclerosis in Brazilian patients

Cited by 16 publications

References 27 publications

Gene-based therapies for neuromuscular disorders

Gene-based therapies for neuromuscular disorders

A Novel Age-Related Circular RNA Circ-ATXN2 Inhibits Proliferation, Promotes Cell Death and Adipogenesis in Rat Adipose Tissue-Derived Stromal Cells

Beyond C9orf72: repeat expansions and copy number variations as risk factors of amyotrophic lateral sclerosis across various populations

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