ArticlePloS one2014
TDP-43 inclusion bodies formed in bacteria are structurally amorphous, non-amyloid and inherently toxic to neuroblastoma cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 84 citations in OpenAlex.
- Engineering a dimeric single-domain antibody for improved detection and neutralization of amyloid-β oligomers.Communications biology · 2026Article
- Understanding liquid-liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation.Genome biology · 2026Review
- Improving our understanding of the biology of aging: findings from the Age-It Research Program.The journals of gerontology. Series B, Psychological sciences and social sciences · 2025Article
- De novo design of protein binders to stabilize monomeric TDP-43 and inhibit its pathological aggregation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Nutraceutical Strategies for Targeting Mitochondrial Dysfunction in Neurodegenerative Diseases.Foods (Basel, Switzerland) · 2025Review
- Review
- The Regulation of TDP-43 Structure and Phase Transitions: A Review.The protein journal · 2025Review
- Biophysical characterization of the phase separation of TDP-43 devoid of the C-terminal domain.Cellular & molecular biology letters · 2024Article
- Protein aggregation and therapeutic strategies in SOD1- and TDP-43- linked ALS.Frontiers in molecular biosciences · 2024Review
- AnAnnals of medicine · 2023Article
- MAPK/MAK/MRK overlapping kinase (MOK) controls microglial inflammatory/type-I IFN responses via Brd4 and is involved in ALS.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The positive impact on translational research of Fondazione italiana di ricerca per la Sclerosi Laterale Amiotrofica (AriSLA), a non-profit foundation focused on amyotrophic lateral sclerosis. Convergence of ex-ante evaluation and ex-post outcomes when goals are set upfront.Frontiers in research metrics and analytics · 2023Article
- Structural polymorphism of the low-complexity C-terminal domain of TDP-43 amyloid aggregates revealed by solid-state NMR.Frontiers in molecular biosciences · 2023Article
- Biophysical characterization of full-length TAR DNA-binding protein (TDP-43) phase separation.Protein science : a publication of the Protein Society · 2022Article
- Misfolded protein oligomers induce an increase of intracellular CaCellular and molecular life sciences : CMLS · 2022Article
- A quantitative biology approach correlates neuronal toxicity with the largest inclusions of TDP-43.Science advances · 2022Article
- Fusion with heat-resistant obscure (Hero) proteins have the potential to improve the molecular property of recombinant proteins.PloS one · 2022Article
- Frontotemporal Dementia and Glucose Metabolism.Frontiers in neuroscience · 2022Review
- TDP-43 Pathology in Alzheimer's Disease.Molecular neurodegeneration · 2021Review
- Parkin beyond Parkinson's Disease-A Functional Meaning of Parkin Downregulation in TDP-43 Proteinopathies.Cells · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation of ubiquitin-positive, tau- and α-synuclein-negative intracellular inclusions of TDP-43 in the central nervous system represents the major hallmark correlated to amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions. Such inclusions have variably been described as amorphous aggregates or more structured deposits having an amyloid structure. Following the observations that bacterial inclusion bodies generally consist of amyloid aggregates, we have overexpressed full-length TDP-43 and C-terminal TDP-43 in E. coli, purified the resulting full-length and C-terminal TDP-43 containing inclusion bodies (FL and Ct TDP-43 IBs) and subjected them to biophysical analyses to assess their structure/morphology. We show that both FL and Ct TDP-43 aggregates contained in the bacterial IBs do not bind amyloid dyes such as thioflavin T and Congo red, possess a disordered secondary structure, as inferred using circular dichroism and infrared spectroscopies, and are susceptible to proteinase K digestion, thus possessing none of the hallmarks for amyloid. Moreover, atomic force microscopy revealed an irregular structure for both types of TDP-43 IBs and confirmed the absence of amyloid-like species after proteinase K treatment. Cell biology experiments showed that FL TDP-43 IBs were able to impair the viability of cultured neuroblastoma cells when added to their extracellular medium and, more markedly, when transfected into their cytosol, where they are at least in part ubiquitinated and phosphorylated. These data reveal an inherently high propensity of TDP-43 to form amorphous aggregates, which possess, however, an inherently high ability to cause cell dysfunction. This indicates that a gain of toxic function caused by TDP-43 deposits is effective in TDP-43 pathologies, in addition to possible loss of function mechanisms originating from the cellular mistrafficking of the protein.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.