English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Most TDP-43 mouse models of ALS do not display cytoplasmic mislocalisation or protein aggregation of TDP-43 in spinal motor neurons  in vivo . Thus, we investigated whether a combination of defective dynein with a TDP-43 mutation could trigger TDP-43 pathology. Using immunohistochemical methods we examined the intracellular motor neuron pathology of the offspring of TDP-43 WT  and TDP-43 M337V  transgenic mice bred to heterozygous  Loa  mice, which carry an autosomal dominant mutation in dynein cytoplasmic 1 heavy chain 1 ( Dync1h1 ). These mice did not exhibit TDP-43 mislocalisation in spinal motor neurons, but the expression of mutant dynein in combination with wildtype human TDP-43 resulted in p62 upregulation and TDP-43 aggregation, thus partially recapitulating the human disease. These findings provide new insights into the possible relationship between dynein and TDP-43 and could prove useful in future studies looking to elucidate the mechanism behind the TDP-43 pathology observed in ALS.

Aberrant dynein function promotes TDP-43 aggregation and upregulation of p62 in male mice harboring transgenic human TDP-43