Novel Curcumin-Diethyl Fumarate Hybrid as a Dualistic GSK-3β Inhibitor/Nrf2 Inducer for the Treatment of Parkinson's Disease.

Curcumin analogues Diethyl fumarate Glycogen synthase kinase-3β Neurodegeneration Nuclear factor-erythroid related factor 2 Oxidative stress Parkinson’s disease

Journal

ACS chemical neuroscience
ISSN: 1948-7193
Titre abrégé: ACS Chem Neurosci
Pays: United States
ID NLM: 101525337

Informations de publication

Date de publication:
02 09 2020
Historique:
pubmed: 15 7 2020
medline: 22 6 2021
entrez: 15 7 2020
Statut: ppublish

Résumé

Common copathogenic factors, including oxidative stress and neuroinflammation, are found to play a vital role in the development of neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). Nowadays, owing to the multifactorial character of the diseases, no effective therapies are available, thus underlying the need for new strategies. Overexpression of the enzyme GSK-3β and downregulation of the Nrf2/ARE pathway are responsible for a decrease in antioxidant defense effects. These pieces of evidence underline the usefulness of dual GSK-3β inhibitors/Nrf2 inducers. In this regard, to design a dual modulator, the structures of a curcumin-based analogue, as GSK-3β inhibitor, and a diethyl fumarate fragment, as Nrf2 inducer, were combined. Among the hybrids,

Identifiants

pubmed: 32663009
doi: 10.1021/acschemneuro.0c00363
pmc: PMC8009478
doi:

Substances chimiques

Fumarates 0
NF-E2-Related Factor 2 0
diethyl fumarate 5WBU5A3E8A
Glycogen Synthase Kinase 3 beta EC 2.7.11.1
Curcumin IT942ZTH98

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2728-2740

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Auteurs

Rita Maria Concetta Di Martino (RMC)

Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.

Letizia Pruccoli (L)

Department for Life Quality Studies, Alma Mater Studiorum - University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy.

Alessandra Bisi (A)

Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.

Silvia Gobbi (S)

Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.

Angela Rampa (A)

Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.

Ana Martinez (A)

Centro de Investigaciones Biologica, CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.

Concepción Pérez (C)

Centro de Investigaciones Biologica, CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.

Loreto Martinez-Gonzalez (L)

Centro de Investigaciones Biologica, CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.

Maria Paglione (M)

Department of Biology, Agriculture and Food Science, National Research Council (CNR), Institute of Biosciences and BioResources (IBBR), Via Pietro Castellino 111, 80131 Naples, Italy.

Elia Di Schiavi (E)

Department of Biology, Agriculture and Food Science, National Research Council (CNR), Institute of Biosciences and BioResources (IBBR), Via Pietro Castellino 111, 80131 Naples, Italy.

Francesca Seghetti (F)

Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.

Andrea Tarozzi (A)

Department for Life Quality Studies, Alma Mater Studiorum - University of Bologna, Corso d'Augusto 237, 47921 Rimini, Italy.

Federica Belluti (F)

Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.

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Classifications MeSH