There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Various missense mutations were identified in TAR DNA-binding protein-43 (TDP-43)
in patients with amyotrophic lateral sclerosis (ALS). To explore the toxic effect
of mutant TDP-43, we generated stable transfection of wild-type and mutant TDP-43
in motor neuron-like cell line. We found that mutant TDP-43 induced mitochondrial
dysfunction, oxidative damage and nuclear accumulation of nuclear factor E2-related
factor 2 (Nrf2). Nrf2 is an indicator and modulator of oxidative stress and is known
to promote the expression of phase || detoxification enzyme including heme oxygenase-1
(HO-1). However, HO-1 was down regulated in cells expressing the mutant TDP-43, and
could not be restored by sulforaphane which is a known stimulator of Nrf2 and phase
|| detoxification enzyme, including HO-1. Nevertheless, sulforaphane reduced the level
of lactate dehydrogenase and lipoperoxidation products in cells expressing TDP-43
mutant. However, sulforaphane could upregulate the expression of HO-1 and NAD(P)H/quinone
oxidoreductase-1 (NQO-1) in cells transfected with the empty vector and the wild-type
TDP-43. Thus, sulforaphane protected cells against mutant TDP-43 independent of Nrf2-antioxidant
response element (ARE) pathway. How mutant TDP-43 reduces expression of HO-1 and prevents
sulforaphane from activating Nrf2 signaling remains to be investigated.
(c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.