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.
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 PDpatients 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.
Authors: Helena Berlamont; Arnout Bruggeman; Eva Bauwens; Charysse Vandendriessche; Elien Clarebout; Junhua Xie; Sofie De Bruyckere; Griet Van Imschoot; Elien Van Wonterghem; Richard Ducatelle; Patrick Santens; Annemieke Smet; Freddy Haesebrouck; Roosmarijn E Vandenbroucke Journal: Int J Mol Sci Date: 2021-10-20 Impact factor: 5.923
Authors: Annadurai Anandhan; Nhat Nguyen; Arjun Syal; Luke A Dreher; Matthew Dodson; Donna D Zhang; Lalitha Madhavan Journal: Aging Dis Date: 2021-07-01 Impact factor: 6.745