Regulation of Glypican 6-mediated Wnt activation maintains TDP-43 nuclear localization in neurons.

ABSTRACT: Abnormalities in TDP-43 (Transactive response DNA-binding protein 43kDa) localization and function span multiple neurodegenerative diseases and are implicated in driving neuronal degeneration and loss. Nuclear pore complex (NPC) abnormalities and disrupted nucleocytoplasmic trafficking (NCT) contribute to TDP-43 mislocalization, but how these cellular changes are initiated in disease is unclear. Glycerophosphodiester phosphodiesterase 2 (GDE2) is a surface glycosylphosphatidylinositol (GPI)-anchor cleaving enzyme that encodes a physiological pathway that ensures NPC integrity, appropriate NCT, and nuclear TDP-43 expression and function in adult neurons by negatively regulating canonical Wnt signaling. Notably, studies of human postmortem tissue and patient-derived neuronal models suggest t

SUBMITTER: Zhang N 

PROVIDER: S-EPMC12485680 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature