S-Glutathionylation of Keap1: A new role for glutathione S-transferase pi in neuronal protection

Andreia Neves Carvalho, Carla Marques, Rita C. Guedes, Margarida Castro-Caldas, Elsa Rodrigues, Jack Van Horssen, Maria João Gama

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57 Citations (Scopus)


Oxidative stress is a key pathological feature of Parkinson's disease (PD). Glutathione S-transferase pi (GSTP) is a neuroprotective antioxidant enzyme regulated at the transcriptional level by the antioxidant master regulator nuclear factor-erythroid 2-related factor 2 (Nrf2). Here, we show for the first time that upon MPTP-induced oxidative stress, GSTP potentiates S-glutathionylation of Kelch-like ECH-associated protein 1 (Keap1), an endogenous repressor of Nrf2, in vivo. S-glutathionylation of Keap1 leads to Nrf2 activation and subsequently increases expression of GSTP. This positive feedback regulatory loop represents a novel mechanism by which GSTP elicits antioxidant protection in the brain.

Original languageEnglish
Pages (from-to)1455-1466
Number of pages12
JournalFEBS letters
Issue number10
Publication statusPublished - 1 May 2016


  • Glutathione S-Transferase pi
  • Nrf2-Keap1 pathway
  • S-glutathionylation

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