Phosphorylated TDP-43 in frontotemporal lobar degeneration and ALS

By M. Hasegawa, T. Arai, T. Nonaka, F. Kametani, Mari Yoshida, Y. Hashizume, Thomas G. Beach, E. Buratti, Francisco E. Baralle, M. Morita and 4 more. Annals of Neurology, 2008

706 citations recorded by the source corpus.

TAR DNA‐binding protein of 43kDa (TDP‐43) is deposited as cytoplasmic and intranuclear inclusions in brains of patients with frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD‐U) and amyotrophic lateral sclerosis (ALS). Previous studies reported that abnormal phosphorylation takes place in deposited TDP‐43. The aim of this study was to identify the phosphorylation sites and responsible kinases, and to clarify the pathological significance of phosphorylation of TDP‐43.

Subfields: Cellular and Molecular Neuroscience, Neurology

View Paper: https://www.semanticscholar.org/paper/fbb79dd785f7b955ea160681ad8abab27a2ac7bf

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In Cellular and Molecular Neuroscience

1. V. Lee
2. John Q. Trojanowski
3. D. Cleveland
4. S. Alberti
5. Dennis W. Dickson
6. D. Dormann

In Neurology

1. M. Polymenidou
2. D. Cleveland
3. Dennis W. Dickson
4. V. Lee
5. John Q. Trojanowski
6. S. Alberti
7. D. Dormann
8. Brittany N. Dugger

Citations in the corpus

• TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. (2010, background): “Using these, S409/410 have been identified as the major sites of phosphorylation on TDP-43 (55) and were found highly phosphorylated in the proposed pathologic 25 kDa CTFs (see below) (53–56).”
• Gains or losses: molecular mechanisms of TDP43-mediated neurodegeneration (2011, background): “By contrast, antibodies that specifically detect TDP43 that is phosphorylated at serine residues 409 and 410 seem to recognize most TDP43 inclusions as well as the truncated 25-kDa TPD43 CTF”
• Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis (2019, background): “Post-translational Modifications The two most pathologically significant common posttranslational modifications (PTMs) in TDP-43 are phosphorylation and ubiquitination (Arai et al., 2006; Neumann et al., 2006, 2009; Hasegawa et al., 2008; Inukai et al., 2008).”
• Liquid-Liquid Phase Separation in Disease. (2019, background): “Aberrant condensation caused by abnormal phosphorylation may also contribute to disease, as TDP-43 is hyperphosphorylated in ALS and FTD brains (63, 82).”
• Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity (2009, background): “Interestingly, just as the inclusions in FTLD-U and ALS are immunoreactive to phosphorylation-specific antibodies toward pS409/S410 (16, 21), so are the inclusions formed by the 25-kDa fragments (Fig.”