Journal article

Zinc induces depletion and aggregation of endogenous TDP-43

Aphrodite Caragounis, Katherine Ann Price, Cynthia PW Soon, Gulay Filiz, Colin L Masters, Qiao-Xin Li, Peter J Crouch, Anthony R White

FREE RADICAL BIOLOGY AND MEDICINE | ELSEVIER SCIENCE INC | Published : 2010

Abstract

Ubiquitinated neuronal aggregates containing TDP-43 are pathological hallmarks in the spectrum of frontotemporal lobar dementia (FTLD) and amyotrophic lateral sclerosis (ALS). In affected neurons, TDP-43 undergoes C-terminal fragmentation, phosphorylation, and ubiquitination and forms aggregates in the cytoplasm or nucleus. Although in vitro studies have been able to recapitulate these features using transfected cell culture models, little is known about the biochemical mechanisms that underlie pathological changes to endogenous TDP-43. As altered metal ion homeostasis and increased oxidative stress are central features of neurodegeneration, including FTLD and ALS, we sought to determine the..

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