• Skip to main content

Parkinson’s Treatment Report

www.ParkinsonsTreatmentReport.com

Nrf2

Systemic activation of Nrf2 pathway in Parkinson’s disease

November 4, 2019

https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.27878

https://www.ncbi.nlm.nih.gov/pubmed/31682033?dopt=Abstract

TITLE:
Systemic activation of Nrf2 pathway in Parkinson’s disease.

DESCRIPTION:
Systemic activation of Nrf2 pathway in Parkinson’s disease.

Mov Disord. 2019 Nov 04;:

Authors: Petrillo S, Schirinzi T, Di Lazzaro G, D’Amico J, Colona VL, Bertini E, Pierantozzi M, Mari L, Mercuri NB, Piemonte F, Pisani A

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.

PMID: 31682033 [PubMed – as supplied by publisher]

PMID:
PubMed:31682033

DATE FOUND:
11/05/19 06:05AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31682033?dopt=Abstract

Antioxidant, Anti-inflammatory, and Neuroprotective Effects of Novel Vinyl Sulfonate Compounds as Nrf2 Activator

July 11, 2019

https://pubs.acs.org/doi/10.1021/acsmedchemlett.9b00163

https://www.ncbi.nlm.nih.gov/pubmed/31312409?dopt=Abstract

TITLE:
Antioxidant, Anti-inflammatory, and Neuroprotective Effects of Novel Vinyl Sulfonate Compounds as Nrf2 Activator.

DESCRIPTION:
Antioxidant, Anti-inflammatory, and Neuroprotective Effects of Novel Vinyl Sulfonate Compounds as Nrf2 Activator.

ACS Med Chem Lett. 2019 Jul 11;10(7):1061-1067

Authors: Choi JW, Shin SJ, Kim HJ, Park JH, Kim HJ, Lee EH, Pae AN, Bahn YS, Park KD

Abstract

The main pathway responsible for cellular regulation against oxidative stress is nuclear factor E2-related factor-2 (Nrf2) signaling. We previously synthesized and reported a novel vinyl sulfone (1) as an Nrf2 activator with therapeutic potential for Parkinson’s disease (PD). In this study, we changed the vinyl sulfone to vinyl sulfonamide or vinyl sulfonate to improve Nrf2 activating efficacy. We observed that the introduction of vinyl sulfonamide led to a reduction of the effects on Nrf2 activation, whereas vinyl sulfonate compounds exhibited superior activity compared to the vinyl sulfone compounds. Among the vinyl sulfonates, 3c exhibited 6.9- and 83.5-fold higher effects on Nrf2 activation than the corresponding vinyl sulfone (1) and vinyl sulfonamide (2c), respectively. Compound 3c was confirmed to induce expression of the Nrf2-dependent antioxidant enzymes at the protein level in cells. In addition, 3c mitigated PD-associated behavioral deficits by protecting DAergic neurons in the MPTP-induced mouse model of PD.

PMID: 31312409 [PubMed]

PMID:
PubMed:31312409

DATE FOUND:
07/18/19 06:03AM

LINK / URL:
https://www.ncbi.nlm.nih.gov/pubmed/31312409?dopt=Abstract

Powered by Urgent Research

Copyright © 2025 Urgent Research