Related Experiment Video

Updated: May 15, 2025

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing
09:02

Protocol for the Differentiation of Human Induced Pluripotent Stem Cells into Mixed Cultures of Neurons and Glia for Neurotoxicity Testing

Published on: June 9, 2017

23.0K

Nrf2 Activation and Antioxidant Properties of Chromone-Containing MTDLs for Alzheimer's Disease Treatment

Alexey Simakov1,2, Stecy Chhor2, Lhassane Ismaili1

  • 1Université Marie et Louis Pasteur, INSERM UMR1322 LINC, F-25000 Besançon, France.

Molecules (Basel, Switzerland)
|May 14, 2025
PubMed

Insights

New multitarget-directed ligands show promise for Alzheimer's disease treatment by activating the Nrf2/ARE pathway and boosting antioxidant defenses. Compound 4d demonstrated significant antioxidant effects, warranting further investigation.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Oxidative Stress Research

Background:

  • Alzheimer's disease (AD) is a progressive neurodegenerative disorder with no cure, significantly impacting global health and economies.
  • Oxidative stress is a key factor in AD pathogenesis, making the Nrf2/ARE pathway a potential therapeutic target.
  • Multitarget-directed ligands (MTDLs) offer a promising strategy for developing effective AD therapeutics.

Purpose of the Study:

  • To evaluate the antioxidant potential of novel chromone-containing MTDLs in vitro.
  • To assess the compounds' ability to activate the Nrf2/ARE pathway and its downstream antioxidant genes.
  • To identify promising MTDL candidates for further Alzheimer's disease drug development.

Main Methods:

  • Synthesis and in vitro evaluation of eight chromone-containing MTDLs.
  • Assay of Nrf2 transcriptional activation and Nrf2/ARE downstream gene expression (NQO1, HO1).
  • In vitro assessment of antioxidant effects of the tested compounds.

Main Results:

  • All tested MTDLs successfully activated the Nrf2/ARE pathway.
  • Compounds 4b, 4c, 4f, and 4h exhibited potent Nrf2 activation.
  • Compounds 4b, 4c, 4d, and 4g significantly induced NQO1 and HO1 expression; compound 4d showed notable in vitro antioxidant activity.

Conclusions:

  • Chromone-based MTDLs effectively activate the Nrf2/ARE pathway, suggesting therapeutic potential for Alzheimer's disease.
  • Compounds 4b, 4c, 4d, and 4g are promising candidates due to their ability to modulate key antioxidant genes.
  • Compound 4d is highlighted as the most promising candidate for further investigation in Alzheimer's disease research.
Keywords:
Alzheimer’s diseaseMTDLsNrf2antioxidant effectchromone

More Related Videos

Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology14:57

Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology

Published on: March 23, 2011

93.9K
Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy07:40

Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy

Published on: May 26, 2023

1.0K

Related Concept Videos

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
9.6K
Alzheimer's Disease: Treatment01:22

Alzheimer's Disease: Treatment

Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
132
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.2K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
76.3K
Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists01:30

Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists

Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function.
85