Poly-GR dipeptide repeat polymers correlate with neurodegeneration and Clinicopathological subtypes in C9ORF72-related brain disease

Acta Neuropathologica Communications
Nobutaka SakaeDennis W Dickson

Abstract

Frontotemporal lobar degeneration (FTLD) is heterogeneous in clinical presentation, neuropathological characteristics and genetics. An expanded GGGGCC hexanucleotide repeat in C9ORF72 is the most common genetic cause of both FTLD and motor neuron disease (MND). Dipeptide repeat polymers (DPR) are generated through repeat-associated non-ATG translation, and they aggregate in neuronal inclusions with a distribution distinct from that of TDP-43 pathology. Recent studies from animal and cell culture models suggest that DPR might be toxic, but that toxicity may differ for specific DPR. Arginine containing DPR (poly-GR and poly-PR) have the greatest toxicity and are less frequent than other DPR (poly-GP, poly-GA). A unique feature of arginine-containing DPR is their potential for post-translational modification by methyl-transferases, which produces methylarginine DPR. In this report, we explored the relationship of DPR and methylarginine to markers of neurodegeneration using quantitative digital microscopic methods in 40 patients with C9ORF72 mutations and one of three different clinicopathologic phenotypes, FTLD, FTLD-MND or MND. We find that density and distribution of poly-GR inclusions are different from poly-GA and poly-GP incl...Continue Reading

References

Jun 15, 2007·Acta Neuropathologica·Dennis W DicksonCatalina Amador-Ortiz
May 21, 2009·Acta Neuropathologica·Keith A JosephsDennis W Dickson
Jan 13, 2011·Acta Neuropathologica·Felix GeserJohn Q Trojanowski
Mar 30, 2011·Nature Reviews. Nephrology·Edzard Schwedhelm, Rainer H Böger
Jun 7, 2011·Acta Neuropathologica·Ian R A MackenzieVirginia M Y Lee
Feb 28, 2013·International Journal of Molecular Sciences·Shufen ChenHans Worthmann
Oct 8, 2013·Acta Neuropathologica·Ian R MackenzieManuela Neumann
Mar 4, 2014·Biochimica Et Biophysica Acta·Sitaram Gayatri, Mark T Bedford
Dec 5, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Melissa E MurrayKejal Kantarci
Feb 13, 2016·Scientific Reports·Steven BoeynaemsLudo Van Den Bosch
Mar 27, 2016·Journal of Neurochemistry·Tiffany W Todd, Leonard Petrucelli
Nov 1, 2016·Brain : a Journal of Neurology·Sarat C VatsavayaiWilliam W Seeley
Nov 26, 2016·Neurochemical Research·Anna CzarneckaMagdalena Zielińska
Mar 1, 2017·Frontiers in Molecular Neuroscience·Brian D Freibaum, J Paul Taylor

❮ Previous
Next ❯

Citations

Oct 29, 2018·Acta Neuropathologica·Sarat C VatsavayaiWilliam W Seeley
Dec 24, 2018·Neuropathology and Applied Neurobiology·B BorroniE Buratti
Feb 16, 2019·Molecular Neurodegeneration·Jeannie ChewLeonard Petrucelli
Mar 29, 2019·Laboratory Investigation; a Journal of Technical Methods and Pathology·Monica Banez-Coronel, Laura P W Ranum
Nov 14, 2019·The EMBO Journal·Bart SwinnenLudo Van Den Bosch
Nov 2, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Jie Jiang, John Ravits
Feb 23, 2020·Molecular & Cellular Proteomics : MCP·Mona RadwanDanny M Hatters
May 31, 2020·International Journal of Molecular Sciences·Yeomin Yun, Yoon Ha
Jun 10, 2020·International Journal of Molecular Sciences·Fiona LimanaqiFrancesco Fornai
Apr 26, 2019·Proceedings of the National Academy of Sciences of the United States of America·Rodrigo Lopez-GonzalezFen-Biao Gao
Aug 27, 2019·Annals of Clinical and Translational Neurology·Nobutaka SakaeDennis W Dickson
Sep 4, 2020·Science Translational Medicine·Casey N CookLeonard Petrucelli
Mar 27, 2019·Annual Review of Neuroscience·Lien NguyenLaura P W Ranum
Jan 17, 2021·Molecular & Cellular Proteomics : MCP·Mona RadwanDanny M Hatters
Mar 9, 2021·Frontiers in Cellular Neuroscience·Alexander SchmitzSmita Saxena
Apr 10, 2021·Frontiers in Cellular Neuroscience·Anna L GillFernando G Vieira
Apr 24, 2021·Brain : a Journal of Neurology·Mariely DeJesus-HernandezMarka van Blitterswijk
May 11, 2021·Frontiers in Cellular Neuroscience·Daniel A SolomonSarah Mizielinska
Oct 26, 2021·Disease Models & Mechanisms·Fréderike W RiemslaghRob Willemsen
Oct 29, 2021·RNA·Natalia B Nedelsky, J Paul Taylor
Jan 4, 2022·Molecular Neurobiology·Maria Isabel Alvarez-MoraLaia Rodriguez-Revenga

❮ Previous
Next ❯

Methods Mentioned

BETA
dissection
co-immunoprecipitation

Software Mentioned

poly
Sigma Plot
Aperio ImageScope
GA

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.