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 language | English |
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Pages (from-to) | 180-184 |
Number of pages | 5 |
Journal | Mov. Disord. |
Volume | 35 |
Issue number | 1 |
DOIs | |
Publication status | Published - 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