The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Repetitive element transcripts are elevated in the brain of C9orf72 ALS/FTLD patients
Open accessAbstract
Significant transcriptome alterations are detected in the brain of patients with amyotrophic lateral sclerosis (ALS), including carriers of the C9orf72 repeat expansion and C9orf72-negative sporadic cases. Recently, the expression of repetitive element transcripts has been associated with toxicity and, while increased repetitive element expression has been observed in several neurodegenerative diseases, little is known about their contribution to ALS. To assess whether aberrant expression of repetitive element sequences are observed in ALS, we analysed RNA sequencing data from C9orf72-positive and sporadic ALS cases, as well as healthy controls. Transcripts from multiple classes and subclasses of repetitive elements (LINEs, endogenous retroviruses, DNA transposons, simple repeats, etc.) were significantly increased in the frontal cortex of C9orf72 ALS patients. A large collection of patient samples, representing both C9orf72 positive and negative ALS, ALS/FTLD, and FTLD cases, was used to validate the levels of several repetitive element transcripts. These analyses confirmed that repetitive element expression was significantly increased in C9orf72-positive compared to C9orf72-negative or control cases. While previous studies suggest an important link between TDP-43 and repetitive element biology, our data indicate that TDP-43 pathology alone is insufficient to account for the observed changes in repetitive elements in ALS/FTLD. Instead, we found that repetitive element expression positively correlated with RNA polymerase II activity in postmortem brain, and pharmacologic modulation of RNA polymerase II activity altered repetitive element expression in vitro. We conclude that increased RNA polymerase II activity in ALS/FTLD may lead to increased repetitive element transcript expression, a novel pathological feature of ALS/FTLD.
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“Prudencio et al. (2017) did not, however, detect a positive correlation between TDP-43 protein pathology burden and retrotransposon expression.”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Prudencio et al. 2017
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“Several substantially larger studies have since confirmed the broad upregulation of retrotransposon sequences in subjects with ALS or FTD”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Prudencio et al. 2017
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“a study from the Petrucelli and Link labs (Prudencio et al. 2017) reported the enrichment of retrotransposon transcripts in a subset of ALS samples from C9orf72 familial disease”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Prudencio et al. 2017
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“In each case, retrotransposon expression was found to be elevated in ALS or FTD samples.”
From The Role of Retrotransposons and Endogenous Retroviruses in Age-Dependent Neurodegenerative Disorders (2024) · cites this paper as Prudencio et al. 2017
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Metadata
- Authors
- Prudencio, M., Gonzales, P. K., Cook, C. N., Gendron, T. F., Daughrity, L. M., Song, Y., Ebbert, M. T. W., van Blitterswijk, M., Zhang, Y.-J., Jansen-West, K., Baker, M. C., DeTure, M., Rademakers, R., Boylan, K. B., Dickson, D. W., Petrucelli, L., & Link, C. D.
- Affiliations
- Mayo Clinic (US)
- Integrative Physiology, Institute for Behavioral Genetics University of Colorado, CO 80309, USA
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
- Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA
- Corresponding author
- Petrucelli, Leonard
- ORCID
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-06-16
- Volume
- 26
- Issue
- 17
- Pages
- 3421-3431
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC5886204
- OpenAlex
- W2626250818
- Cited by
- 122
- References
- 54
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 11 · 2023: 14 · 2022: 13 · 2021: 13 · 2020: 11 · 2019: 18 · 2018: 13 · 2017: 3
- FWCI
- 8.57
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Human Molecular Genetics (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- NIH
- National Institute of Neurological Disorders and Stroke
- NINDS (R01NS063964, R21NS089979, R35NS097273, R21NS084528, P01NS084974, P01NS099114, R01NS088689, R01NS093865, R35NS097261, R01NS080882)
- Department of Defense (AL130125)
- Amyotrophic Lateral Sclerosis Association
- Association for Frontotemporal Degeneration
- Muscular Dystrophy Association (#416137)
- National Center for Advancing Translational Sciences
- NCATS
- Topics
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Keywords
- amyotrophic lateral sclerosis, frontotemporal lobar degeneration, C9orf72 repeat expansion, TDP-43, lines, endogenous retroviruses, DNA transposons, simple repeats, frontal cortex, neurodegeneration, pharmacological modulation
- MeSH terms
- C9orf72 Protein, Aged, Amyotrophic Lateral Sclerosis, Autopsy, Brain, Female, Frontal Lobe, Heterozygote, Humans, Male, Middle Aged, Mutation, Repetitive Sequences, Nucleic Acid, RNA Polymerase II, Transcriptional Activation, Case-Control Studies, Sequence Analysis, RNA, Neurodegenerative Diseases, DNA Repeat Expansion, Frontotemporal Lobar Degeneration
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