Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis

By M. Neumann, Deepak M. Sampathu, L. Kwong, A. Truax, M. Micsenyi, T. T. Chou, J. Bruce, T. Schuck, Murray C. Grossman, Christopher M. Clark and 9 more. Science, 2006

6,344 citations recorded by the source corpus.

Subfields: Neurology

View Paper: https://www.semanticscholar.org/paper/f0c6ade907d1549199e22221230c465ad5e0fa1a

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In Neurology

Citations in the corpus

ALS‐associated fused in sarcoma (FUS) mutations disrupt Transportin‐mediated nuclear import (2010, background): “…normally reside and function predominantly in the nucleus, pathological FUS and TDP-43 inclusions are mostly observed in the cytosol, and inclusion-bearing cells often show a reduction of nuclear staining (Arai et al, 2006; Neumann et al, 2006, 2009a; Kwiatkowski et al, 2009; Vance et al, 2009).”
Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for Frontotemporal Lobar Degeneration (2007, background): “areas with ubiquitin-immunoreactive inclusions including hippocampus, neocortex, and spinal cord [61].”
Non–cell autonomous toxicity in neurodegenerative disorders: ALS and beyond (2009, background): “Moreover, TDP-43 misaccumulation in motor neurons and astrocytes (Neumann et al., 2006; Cairns et al., 2007) is seen in most instances of sporadic or familial ALS, so noncellautonomous disease seems likely to be a universal feature of ALS.”
ALS mutations disrupt phase separation mediated by -helical structure in the TDP-43 low complexity C-terminal domain (2016, background): “TDP-43 remains a primary target in neurodegenerative disease research because of its aggregate pathology and role in ALS, frontotemporal dementia(Neumann et al., 2006), and Alzheimer’s disease (Amador-Ortiz et al.”
Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis (2019, background): “In 2006, TDP-43 was identified as a key component of the insoluble and ubiquitinated inclusions in the brains of patients suffering from amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD or FTLD-TDP) diseases (Arai et al., 2006; Neumann et al., 2006).”
Oxidative stress in ALS: key role in motor neuron injury and therapeutic target. (2010, neutral): “[142,143].”
Cell-free formation of RNA granules: bound RNAs identify features and components of cellular assemblies. (2012, background): “There is no question that these LCdomains can enter into irreversible fibrous aggregates, just as happens with the LC domains housed within many gene products associated with neurodegenerative disease (Koyano et al., 1999; Kwiatkowski et al., 2009; Neumann et al., 2006; Vance et al., 2009).”
Expanded GGGGCC hexanucleotide repeat in non-coding region of C9ORF72 causes chromosome 9p-linked frontotemporal dementia and amyotrophic lateral sclerosis (2011, positive): “…DNA binding protein with M r 43 kD (TDP-43) as the pathological protein in the vast majority of ALS cases and in the most common pathological subtype of FTD (Neumann et al., 2006) (now referred to as frontotemporal lobar degeneration with TDP-43 pathology, FTLD-TDP) (Mackenzie et al., 2009).”
Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. (2013, positive): “Protein was sequentially extracted from frozen cerebellar tissue as previously described by Neumann et al. (2006).”
TDP‐43 regulates its mRNA levels through a negative feedback loop (2011, background): “…modification of TDP-43 are key markers for a group of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) (Arai et al, 2006; Neumann et al, 2006), now also referred to as TDP-43 proteinopathies.”
TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration (2009, background): “Furthermore, C-terminal fragments of TDP-43 are observed selectively in ALS and FTLD-U tissues, suggesting that proteolytic cleavage of TDP-43 leads to protein aggregation or another toxic property (6).”
Amyotrophic lateral sclerosis: a clinical review (2020, background): “TDP-43 is the main component of these inclusions in more than 95% of ALS patients [7].”
Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS (2010, neutral): “These studies indicate that Ataxin-2 localization is altered in spinal cord neurons of ALS patients (see Supplemental Results for further analysis of Ataxin-2 localization in FTLD-TDP and TDP-43 analysis in SCA2).”