Role of Nrf2 in Synaptic Plasticity and Memory in Alzheimer’s Disease

Davies, Don A.; Adlimoghaddam, Aida; Albensi, Benedict C.

doi:10.3390/cells10081884

Cited by 51 publications

(33 citation statements)

References 220 publications

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“…Our data indicate that oxidation is an early event in the pathogenesis of ChAc in Vps13a −/− mice, resembling other neurodegenerative disorders such as PD or AD [ 18 , 51 , 52 , 54 ]. Indeed, protein oxidation was detectable in basal ganglia from 12-month-old Vps13a −/− mice, whereas neuronal loss appeared not earlier than in 18 months old Vps13a −/− mice.…”

Section: Discussionmentioning

confidence: 53%

“…NRF2 is a key redox-related transcription factor, linked to PRXs expression and function [ 11 ]. Studies of neurodegenerative disorders such as PD or AD have shown oxidation to be an early neurotoxicity marker of abnormal proteostasis [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. We observed age-dependent increases in protein oxidation in basal ganglia isolated from Vps13a −/− and wild-type mice of ages 12 and 18 months, as determined by OxyBlot ( Figure 2 a and Figure S2 ).…”

Section: Resultsmentioning

confidence: 99%

“…To investigate the possibility that potentiation of cytoprotective systems can counteract oxidation in neurodegenerative disorders, different therapeutic strategies to restore redox balance have been tested in both cell and animal models of AD, PD and multiple sclerosis (MS) [ 51 , 52 ]. These strategies are based largely on pure antioxidants (such as N-acetylcysteine and ω3-fatty acid supplementation), or antioxidant/potentiators of NRF2 (such as quercitin and myricytin), or NRF2 antagonists (e.g., sulphoraphane and dimethylfumarate) [ 51 , 52 , 58 ]. Although beneficial antioxidant effects of these molecules have been reported in models for neurodegenerative disorders, the time of treatment initiation during the course of disease progression seems to be an important determinant of treatment impact.…”

Section: Discussionmentioning

confidence: 99%

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Adaptative Up-Regulation of PRX2 and PRX5 Expression Characterizes Brain from a Mouse Model of Chorea-Acanthocytosis

et al. 2021

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The peroxiredoxins (PRXs) constitute a ubiquitous antioxidant. Growing evidence in neurodegenerative disorders such as Parkinson’s disease (PD) or Alzheimer’s disease (AD) has highlighted a crucial role for PRXs against neuro-oxidation. Chorea-acanthocytosis/Vps13A disease (ChAc) is a devastating, life-shortening disorder characterized by acanthocytosis, neurodegeneration and abnormal proteostasis. We recently developed a Vps13a−/− ChAc-mouse model, showing acanthocytosis, neurodegeneration and neuroinflammation which could be restored by LYN inactivation. Here, we show in our Vps13a−/− mice protein oxidation, NRF2 activation and upregulation of downstream cytoprotective systems NQO1, SRXN1 and TRXR in basal ganglia. This was associated with upregulation of PRX2/5 expression compared to wild-type mice. PRX2 expression was age-dependent in both mouse strains, whereas only Vps13a−/− PRX5 expression was increased independent of age. LYN deficiency or nilotinib-mediated LYN inhibition improved autophagy in Vps13a−/− mice. In Vps13a−/−; Lyn−/− basal ganglia, absence of LYN resulted in reduced NRF2 activation and down-regulated expression of PRX2/5, SRXN1 and TRXR. Nilotinib treatment of Vps13a−/− mice reduced basal ganglia oxidation, and plasma PRX5 levels, suggesting plasma PRX5 as a possible ChAc biomarker. Our data support initiation of therapeutic Lyn inhibition as promptly as possible after ChAc diagnosis to minimize development of irreversible neuronal damage during otherwise inevitable ChAc progression.

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Section: Discussionmentioning

confidence: 53%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Adaptative Up-Regulation of PRX2 and PRX5 Expression Characterizes Brain from a Mouse Model of Chorea-Acanthocytosis

et al. 2021

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“…Therefore, the increase in BDNF in the hippocampus of TB animals could be related to the beneficial effect of CUR on memory and the decrease in depression-like behavior in this model. Another factor that protects the brain from injury is Nrf2, as oxidative damage plays a critical role in many central nervous system diseases [93]. CUR protected from injury in a model of an ischemic brain through the Akt/Nrf2 pathway [94].…”

Section: Discussionmentioning

confidence: 99%

Effect of Curcumin in Experimental Pulmonary Tuberculosis: Antimycobacterial Activity in the Lungs and Anti-Inflammatory Effect in the Brain

Lara-Espinosa

Arce-Aceves

López-Torres

et al. 2022

IJMS

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Tuberculosis (TB) is one of the ten leading causes of death worldwide. Patients with TB have been observed to suffer from depression and anxiety linked to social variables. Previous experiments found that the substantial pulmonary inflammation associated with TB causes neuroinflammation, neuronal death, and behavioral impairments in the absence of brain infection. Curcumin (CUR) is a natural product with antioxidant, anti-inflammatory and antibacterial activities. In this work, we evaluated the CUR effect on the growth control of mycobacteria in the lungs and the anti-inflammatory effect in the brain using a model of progressive pulmonary TB in BALB/c mice infected with drug-sensitive mycobacteria (strain H37Rv). The results have shown that CUR decreased lung bacilli load and pneumonia of infected animals. Finally, CUR significantly decreased neuroinflammation (expression of TNFα, IFNγ and IL12) and slightly increased the levels of nuclear factor erythroid 2-related to factor 2 (Nrf2) and the brain-derived neurotrophic factor (BDNF) levels, improving behavioral status. These results suggest that CUR has a bactericidal effect and can control pulmonary mycobacterial infection and reduce neuroinflammation. It seems that CUR has a promising potential as adjuvant therapy in TB treatment.

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“…Furthermore, SMOX activity not only controls Spm/Spd cellular ratio, but it is also a source of cellular redox alteration by producing H 2 O 2 , a reactive oxygen species (ROS). Hydrogen peroxide can also modulate brain Long-Term Potentiation in a dose-dependent manner, but an excessive increase of it can result in learning and memory impairment [ 27 ]. Spermine oxidation by SMOX is also responsible for secondary tissue damage, due to the generation of 3-AP, which spontaneously converts into acrolein [ 11 , 28 ].…”

Section: The Smox Overexpressing Mouse: An Animal Model Of Chronic Sp...mentioning

confidence: 99%

Transgenic Mouse Overexpressing Spermine Oxidase in Cerebrocortical Neurons: Astrocyte Dysfunction and Susceptibility to Epileptic Seizures

et al. 2022

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Polyamines are organic polycations ubiquitously present in living cells. Polyamines are involved in many cellular processes, and their content in mammalian cells is tightly controlled. Among their function, these molecules modulate the activity of several ion channels. Spermine oxidase, specifically oxidized spermine, is a neuromodulator of several types of ion channel and ionotropic glutamate receptors, and its deregulated activity has been linked to several brain pathologies, including epilepsy. The Dach-SMOX mouse line was generated using a Cre/loxP-based recombination approach to study the complex and critical functions carried out by spermine oxidase and spermine in the mammalian brain. This mouse genetic model overexpresses spermine oxidase in the neocortex and is a chronic model of excitotoxic/oxidative injury and neuron vulnerability to oxidative stress and excitotoxic, since its phenotype revealed to be more susceptible to different acute oxidative insults. In this review, the molecular mechanisms underlined the Dach-SMOX phenotype, linked to reactive astrocytosis, neuron loss, chronic oxidative and excitotoxic stress, and susceptibility to seizures have been discussed in detail. The Dach-SMOX mouse model overexpressing SMOX may help in shedding lights on the susceptibility to epileptic seizures, possibly helping to understand the mechanisms underlying epileptogenesis in vulnerable individuals and contributing to provide new molecular mechanism targets to search for novel antiepileptic drugs.

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Role of Nrf2 in Synaptic Plasticity and Memory in Alzheimer’s Disease

Cited by 51 publications

References 220 publications

Adaptative Up-Regulation of PRX2 and PRX5 Expression Characterizes Brain from a Mouse Model of Chorea-Acanthocytosis

Adaptative Up-Regulation of PRX2 and PRX5 Expression Characterizes Brain from a Mouse Model of Chorea-Acanthocytosis

Effect of Curcumin in Experimental Pulmonary Tuberculosis: Antimycobacterial Activity in the Lungs and Anti-Inflammatory Effect in the Brain

Transgenic Mouse Overexpressing Spermine Oxidase in Cerebrocortical Neurons: Astrocyte Dysfunction and Susceptibility to Epileptic Seizures

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