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TDP-43 Is Efficient...
TDP-43 Is Efficiently Transferred Between Neuron-Like Cells in a Manner Enhanced by Preservation of Its N-Terminus but Independent of Extracellular Vesicles
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- Sackmann, Christopher, 1988- (författare)
- Linköpings universitet,Avdelningen för neurobiologi,Medicinska fakulteten,Region Östergötland, Klinisk patologi
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- Sackmann, Valerie, 1990- (författare)
- Linköpings universitet,Avdelningen för neurobiologi,Medicinska fakulteten,Region Östergötland, Klinisk patologi
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- Hallbeck, Martin, 1970- (författare)
- Linköpings universitet,Avdelningen för neurobiologi,Medicinska fakulteten,Region Östergötland, Klinisk patologi
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(creator_code:org_t)
- 2020-06-11
- 2020
- Engelska.
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Ingår i: Frontiers in Neuroscience. - : FRONTIERS MEDIA SA. - 1662-4548 .- 1662-453X. ; 14
- Relaterad länk:
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https://www.frontier...
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visa fler...
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https://urn.kb.se/re...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- The misfolding of transactive response DNA-binding protein (TDP-43) is a major contributor to the pathogenesis of TDP-43 proteinopathies, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration with TDP-43 inclusions, but also plays a role in other neurodegenerative diseases including Alzheimer disease. It is thought that different truncations at the N- and C-termini of TDP-43 contribute to its misfolding and aggregation in the brain, and that these aberrant TDP-43 fragments contribute to disease. Despite this, little is known about whether different truncation events influence the proteins transmissibility between cells and how this cell-to-cell transfer occurs. In this study, we use a well-established cellular model to study the efficiency by which full-length and truncated TDP-43 fragments are transferred between neuron-like cells. We demonstrate that preservation of the N-terminus of TDP-43 enhances its transmissibility between cells and that this protein transmission occurs in a manner exclusive of extracellular vesicles, instead requiring cellular proximity for efficient propagation. These data indicate that the N-terminus of TDP-43 might be a useful target in the generation of therapeutics to limit the spread of TDP-43 pathology.
Ämnesord
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Nyckelord
- TDP-43; extracellular vesicles; C-terminus; N-terminus; cell-to-cell; protein transfer; amyotrophic lateral sclerosis; frontotemporal lobar degeneration
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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