Systemic activation of Nrf2 pathway in Parkinson's disease

Sara Petrillo, Tommaso Schirinzi, Giulia Di Lazzaro, Jessica D'Amico, Vito L. Colona, Enrico Bertini, Mariangela Pierantozzi, Luisa Mari, Nicola B. Mercuri, Fiorella Piemonte, Antonio Pisani

Research output: Contribution to journalArticle

Abstract

Background: Preclinical studies underlined the relevance of Nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor pathway in the pathogenesis of Parkinson's disease (PD). Objective: The objective of this study was to explore Nrf2 pathway in vivo in PD, looking for novel disease biomarkers and therapeutic targets. Methods: The levels of Nrf2, the downstream effectors (NAD(P)H dehydrogenase [quinone] 1 (Nqo1) enzyme, glutathione metabolism enzymes Glutamate–cysteine ligase (GCL) and Glutathione Reductase (GR)), the upstream activators (redox state and mitochondrial dysfunction), and α-synuclein oligomers were assessed in the blood leukocytes of PD patients comparatively to controls. Biochemical data were correlated to clinical parameters. Results: In PD, Nrf2 was highly transcribed and expressed as well as its target effectors. The mitochondrial complex I activity was reduced and the oxidized form of glutathione prevailed, disclosing the presence of pathway's activators. Also, α-synuclein oligomers levels were increased. Nrf2 transcript and oligomers levels correlated with PD duration. Conclusions: Blood leukocytes mirror pathogenic mechanisms of PD, showing the systemic activation of the Nrf2 pathway and its link with synucleinopathy and clinical events.

Original languageEnglish
JournalMovement Disorders
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Parkinson Disease
Synucleins
Leukocytes
NAD(P)H Dehydrogenase (Quinone)
Glutathione Disulfide
Glutathione Reductase
Enzymes
Ligases
Oxidation-Reduction
Glutathione
Transcription Factors
Biomarkers

Keywords

  • biomarkers
  • Nrf2
  • oxidative stress
  • Parkinson's disease
  • synuclein

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Systemic activation of Nrf2 pathway in Parkinson's disease. / Petrillo, Sara; Schirinzi, Tommaso; Di Lazzaro, Giulia; D'Amico, Jessica; Colona, Vito L.; Bertini, Enrico; Pierantozzi, Mariangela; Mari, Luisa; Mercuri, Nicola B.; Piemonte, Fiorella; Pisani, Antonio.

In: Movement Disorders, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "Background: Preclinical studies underlined the relevance of Nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor pathway in the pathogenesis of Parkinson's disease (PD). Objective: The objective of this study was to explore Nrf2 pathway in vivo in PD, looking for novel disease biomarkers and therapeutic targets. Methods: The levels of Nrf2, the downstream effectors (NAD(P)H dehydrogenase [quinone] 1 (Nqo1) enzyme, glutathione metabolism enzymes Glutamate–cysteine ligase (GCL) and Glutathione Reductase (GR)), the upstream activators (redox state and mitochondrial dysfunction), and α-synuclein oligomers were assessed in the blood leukocytes of PD patients comparatively to controls. Biochemical data were correlated to clinical parameters. Results: In PD, Nrf2 was highly transcribed and expressed as well as its target effectors. The mitochondrial complex I activity was reduced and the oxidized form of glutathione prevailed, disclosing the presence of pathway's activators. Also, α-synuclein oligomers levels were increased. Nrf2 transcript and oligomers levels correlated with PD duration. Conclusions: Blood leukocytes mirror pathogenic mechanisms of PD, showing the systemic activation of the Nrf2 pathway and its link with synucleinopathy and clinical events.",
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AU - Schirinzi, Tommaso

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AU - Colona, Vito L.

AU - Bertini, Enrico

AU - Pierantozzi, Mariangela

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AU - Mercuri, Nicola B.

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