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Review
. 2022 May 31;15(6):692.
doi: 10.3390/ph15060692.

A Pivotal Role of Nrf2 in Neurodegenerative Disorders: A New Way for Therapeutic Strategies

Sibel Suzen  1 , Paolo Tucci  2 , Elisabetta Profumo  3 , Brigitta Buttari  3 , Luciano Saso  4
Affiliations
Review

A Pivotal Role of Nrf2 in Neurodegenerative Disorders: A New Way for Therapeutic Strategies

Sibel Suzen et al. Pharmaceuticals (Basel). .

Abstract

Clinical and preclinical research indicates that neurodegenerative diseases are characterized by excess levels of oxidative stress (OS) biomarkers and by lower levels of antioxidant protection in the brain and peripheral tissues. Dysregulations in the oxidant/antioxidant balance are known to be a major factor in the pathogenesis of neurodegenerative diseases and involve mitochondrial dysfunction, protein misfolding, and neuroinflammation, all events that lead to the proteostatic collapse of neuronal cells and their loss. Nuclear factor-E2-related factor 2 (Nrf2) is a short-lived protein that works as a transcription factor and is related to the expression of many cytoprotective genes involved in xenobiotic metabolism and antioxidant responses. A major emerging function of Nrf2 from studies over the past decade is its role in resistance to OS. Nrf2 is a key regulator of OS defense and research supports a protective and defending role of Nrf2 against neurodegenerative conditions. This review describes the influence of Nrf2 on OS and in what way Nrf2 regulates antioxidant defense for neurodegenerative conditions. Furthermore, we evaluate recent research and evidence for a beneficial and potential role of specific Nrf2 activator compounds as therapeutic agents.

Keywords: ALS; Alzheimer’s disease; Huntington’s disease; Nrf2; Parkinson’s disease; antioxidant; neurodegenerative; oxidative stress.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical formula of (a) anetol, (b) anethole trithione, (c) flavon, (d) isothiocyanates, (e) curcumin.
Figure 2
Figure 2
Chemical formula of lanabecestat.
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Figure 3
Chemical formula of (a) Andrographolide (Andro) and (b) carnosic acid (CA).
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Figure 4
Chemical formula of methysticin.
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Figure 5
Chemical formula of (a) sulforaphane, (b) allicin and (c) [(4-tert-butylcyclohexylidene)methyl] (4-methoxystyryl)sulfide (BMMS).
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Figure 6
Chemical formula of (a) 3-n-butylphthalide and (b) pseudoginsenoside-F11.
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Figure 7
Chemical formula of (a) L-dopa, (b) chalcone, and (c) dimethyl fumarate.
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Figure 8
Chemical formula of (a) isothiocyanate (A: S=O, C=O, C-OH) derivatives (b) indole derivatives (R: H or CH3).
Figure 9
Figure 9
Chemical formula of (a) Epigallocatechin gallate, (b) Tert-butylhydroquinone (tBHQ), (c) Fucoidan, (d) Pyridoxine.
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Figure 10
Chemical formula of (a) celastrol and (b) trehalose.
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Figure 11
Chemical formula of (a) Dimethyl fumarate (DMF), (b) resveratrol, (c) quercetin, (d) ferulic and (e) lycopene.
Figure 12
Figure 12
Chemical formula of (a) riluzole, (b) edaravone and (c) vitamin E.
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Figure 13
Chemical formula of (a) beta carotene and (b) pterostilbene.
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Figure 14
Chemical formula of (a) fasudil, (b) 11-keto-beta-boswellic acid, and (c) tetramethylpyrazine nitrone.
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