Systemic activation of Nrf2 pathway in Parkinson's disease: Movement Disorders

S. Petrillo, T. Schirinzi, G. Di Lazzaro, J. D'Amico, V.L. Colona, E. Bertini, M. Pierantozzi, L. Mari, N.B. Mercuri, F. Piemonte, A. Pisani

Research output: Contribution to journalArticlepeer-review

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. © 2019 International Parkinson and Movement Disorder Society. © 2019 International Parkinson and Movement Disorder Society
Original languageEnglish
Pages (from-to)180-184
Number of pages5
JournalMov. Disord.
Volume35
Issue number1
DOIs
Publication statusPublished - 2020

Keywords

  • biomarkers
  • Nrf2
  • oxidative stress
  • Parkinson's disease
  • synuclein
  • alpha synuclein
  • biological marker
  • glutamate cysteine ligase
  • glutathione
  • glutathione disulfide
  • glutathione reductase
  • messenger RNA
  • nad(p)h dehydrogenase [quinone] 1
  • oxidoreductase
  • reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone)
  • transcription factor Nrf2
  • unclassified drug
  • NFE2L2 protein, human
  • reactive oxygen metabolite
  • adult
  • Article
  • clinical article
  • clinical feature
  • controlled study
  • enzyme activity
  • enzyme linked immunosorbent assay
  • female
  • glutathione metabolism
  • human
  • human cell
  • in vivo study
  • leukocyte
  • male
  • middle aged
  • Parkinson disease
  • pathogenesis
  • priority journal
  • protein targeting
  • real time polymerase chain reaction
  • signal transduction
  • Western blotting
  • aged
  • animal
  • metabolism
  • parkinsonism
  • pathophysiology
  • physiology
  • Adult
  • Aged
  • alpha-Synuclein
  • Animals
  • Glutathione
  • Humans
  • Male
  • Middle Aged
  • NF-E2-Related Factor 2
  • Oxidative Stress
  • Parkinson Disease
  • Parkinsonian Disorders
  • Reactive Oxygen Species
  • Signal Transduction

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