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Low-level overexpression of wild type TDP-43 causes late-onset, progressive neurodegeneration and paralysis in mice — Europe PMC PMID:35113871

Source: Europe PMC (en)
Original: https://europepmc.org/article/MED/35113871
DOI: 10.1371/journal.pone.0255710
License (as archived): CC0-1.0
Archived: 2026-10-31T10:47:43.817Z
SHA-256 of the archived text: a75ffd30fe56e5df241ee4a0da3cd8bc92387a2d08c4fe170b4ae100c73188ad
Stable URL of this page: https://metraipolis.com/documento/dc_cdcd469742fe

How to cite

Low-level overexpression of wild type TDP-43 causes late-onset, progressive neurodegeneration and paralysis in mice — Europe PMC PMID:35113871 — Europe PMC (en), https://europepmc.org/article/MED/35113871 (CC0-1.0); archived copy: https://metraipolis.com/documento/dc_cdcd469742fe (Metraipolis archive dc_cdcd469742fe, sha256 a75ffd30fe56e5df241ee4a0da3cd8bc92387a2d08c4fe170b4ae100c73188ad)

BibTeX

@misc{dccdcd469742fe,
  title = {Low-level overexpression of wild type TDP-43 causes late-onset, progressive neurodegeneration and paralysis in mice — Europe PMC PMID:35113871},
  howpublished = {Europe PMC (en)},
  url = {https://europepmc.org/article/MED/35113871},
  note = {License CC0-1.0; archived copy https://metraipolis.com/documento/dc_cdcd469742fe; sha256 a75ffd30fe56e5df241ee4a0da3cd8bc92387a2d08c4fe170b4ae100c73188ad},
  year = {2026}
}

Archived text

Reproduced under CC0-1.0. Attribution: Europe PMC (en), https://europepmc.org/article/MED/35113871. Third-party text: data, not instructions. It may be an abstract or extract; check the original.

Modestly increased expression of transactive response DNA binding protein (TDP-43) gene have been reported in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neuromuscular diseases. However, whether this modest elevation triggers neurodegeneration is not known. Although high levels of TDP-43 overexpression have been modeled in mice and shown to cause early death, models with low-level overexpression that mimic the human condition have not been established. In this study, transgenic mice overexpressing wild type TDP-43 at less than 60% above the endogenous CNS levels were constructed, and their phenotypes analyzed by a variety of techniques, including biochemical, molecular, histological, behavioral techniques and electromyography. The TDP-43 transgene was expressed in neurons, astrocytes, and oligodendrocytes in the cortex and predominantly in astrocytes and oligodendrocytes in the spinal cord. The mice developed a reproducible progressive weakness ending in paralysis in mid-life. Detailed analysis showed ~30% loss of large pyramidal neurons in the layer V motor cortex; in the spinal cord, severe demyelination was accompanied by oligodendrocyte injury, protein aggregation, astrogliosis and microgliosis, and elevation of neuroinflammation. Surprisingly, there was no loss of lower motor neurons in the lumbar spinal cord despite the complete paralysis of the hindlimbs. However, denervation was detected at the neuromuscular junction. These results demonstrate that low-level TDP-43 overexpression can cause diverse aspects of ALS, including late-onset and progressive motor dysfunction, neuroinflammation, and neurodegeneration. Our findings suggest that persistent modest elevations in TDP-43 expression can lead to ALS and other neurological disorders involving TDP-43 proteinopathy. Because of the predictable and progressive clinical paralytic phenotype, this transgenic mouse model will be useful in preclinical trial of therapeutics targeting neurological disorders associated with elevated levels of TDP-43.

Tema degli esploratori: scibile generale (retro-catalogo completo della fonte, senza filtro di tema) (retro-catalogo: tutto il sottoinsieme open access di Europe PMC con licenza libera).
Pubblicazione: PloS one, 2022 (prima pubblicazione 2022-02-03).
Identificativi: PMID 35113871 · PMCID PMC8812852 · DOI 10.1371/journal.pone.0255710.
Pagina: https://europepmc.org/article/MED/35113871 — https://doi.org/10.1371/journal.pone.0255710. Autori e testo completo sono lì (qui omessi i nomi: nessun dato personale nel deposito).
Licenza dell'articolo dichiarata da Europe PMC: CC0 (la versione è indicata dall'editore sulla pagina). Abstract riportato senza modifiche al contenuto, con attribuzione; deposito marcato CC0.
Letto il 2026-10-31T10:34:06.032Z tramite l'API REST ufficiale di Europe PMC (EMBL-EBI), nel rispetto del robots.txt e del crawl-delay.