Activation of the Nrf2 Pathway Prevents Mitochondrial Dysfunction Induced by Caspase-3 Cleaved Tau: Implications for Alzheimer’s Disease

Villavicencio-Tejo, Francisca; Olesen, Margrethe A.; Aránguiz, Alejandra; Quintanilla, Rodrigo A.

doi:10.3390/antiox11030515

Cited by 16 publications

(11 citation statements)

References 67 publications

(113 reference statements)

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“…Caspase-8, -3, and -7 in mice can be activated in microglia in the brain of AD patients . Caspase-3 can not only cause A in the brain, β-plaque formation can also cleave the expression of tau, reduce mitochondrial transport in hippocampal neurons, and form synaptic defects . Overall, these studies emphasize the role of apoptotic molecules in the pathogenesis of AD.…”

Section: Resultsmentioning

confidence: 84%

Borneol-Modified Schisandrin B Micelles Cross the Blood–Brain Barrier To Treat Alzheimer’s Disease in Aged Mice

Li,

Yu,

et al. 2024

ACS Chem. Neurosci.

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Objective: Schisandrin B (Sch B) is a bioactive dibenzocyclooctadiene derizative that is prevalent in the fruit of Schisandra chinensis. Numerous studies have demonstrated that Sch B has a neuroprotective action by reducing oxidative stress and effectively preventing inflammation. It follows that Sch B is a potential treatment for Alzheimer's disease (AD). However, the drug's solubility, bioavailability, and lower permeability of the blood−brain barrier (BBB) can all reduce its efficacy during the therapy process. Therefore, this study constructed borneolmodified schisandrin B micelles (Bor-Sch B-Ms), which increase brain targeting by accurately delivering medications to the brain, effectively improving bioavailability. High therapeutic efficacy has been achieved at the pathological site. Methods: Bor-Sch B-Ms were prepared using the thin film dispersion approach in this article. On the one hand, to observe the targeting effect of borneol, we constructed a blood−brain barrier (BBB) model in vitro and studied the ability of micelles to cross the BBB. On the other hand, the distribution of micelle drugs and their related pharmacological effects on neuroinflammation, oxidative stress, and neuronal damage were studied through in vivo administration in mice. Results: In vitro studies have demonstrated that the drug uptake of bEnd.3 cells was increased by the borneol alteration on the surface of the nano micelles, implying that Bor-Sch B-Ms can promote the therapeutic effect of N 2 a cells. This could result in more medicines entering the BBB. In addition, in vivo studies revealed that the distribution and circulation time of medications in the brain tissue were significantly higher than those in other groups, making it more suitable for the treatment of central nervous system diseases. Conclusion: As a novel nanodrug delivery system, borneol modified schisandrin B micelles have promising research prospects in the treatment of Alzheimer's disease.

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Section: Resultsmentioning

confidence: 84%

Borneol-Modified Schisandrin B Micelles Cross the Blood–Brain Barrier To Treat Alzheimer’s Disease in Aged Mice

Li,

Yu,

et al. 2024

ACS Chem. Neurosci.

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“…For example, it interferes with Aβ and p-tau pathways which could be a promising therapeutic option for AD treatment [148]. Due to Nrf2's involvement in oxidative injury, inflammation, and the direct or indirect influence it has on autophagy, the association between decreased Nrf2 and AD could be described [149][150][151][152]. In experimental research of AD, Nrf2 levels were found to be lower by Rojo et al (2017) and Joshi et al (2015), and aggregate-like pathology was shown to increase the relationship between Nrf2 and AD [151,153].…”

Section: The Neuroprotective Effects Of Que On Admentioning

confidence: 99%

Targeting Nrf2 signaling pathway by quercetin in the prevention and treatment of neurological disorders: An overview and update on new developments

Zamanian

Soltani

Khodarahmi

et al. 2023

Fundamemntal Clinical Pharma

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Background: Neurological disorders (NLDs) are widely acknowledged as a significant public health concern worldwide. Stroke, Alzheimer's disease (AD), and traumatic brain injury (TBI) are three of these disorders that have sparked major study attention. Neurological dysfunction, protein buildup, oxidation and neuronal injury, and aberrant mitochondria are all prevalent neuropathological hallmarks of these disorders. The signaling cascade of nuclear factor erythroid 2 related factor 2 (Nrf2) shares all of them as a common target. Several studies have found that overexpression of Nrf2 is a promising treatment method in NLDs. Effective treatment of these disorders continues to be a universal concern regardless of various medicines. In order to treat a variety of neurological problems, organic remedies may provide an alternative treatment. It has been demonstrated that polyphenols like quercetin (Que) offer considerable capabilities for treating NLDs. One of Que's greatest key targets, Nrf2, has the capacity to control the production of a number of cytoprotective enzymes that exhibit neuroprotective, detoxifying, and antioxidative effects. Additionally, Que enhanced the expression of Nrf2 and inhibited alterations in the shape and death of neurons in the hippocampus. Objective: In this review, we have focused on Que's medicinal prospects as a neuroprotective drug. Methods: PubMed, Scopus, Science Direct, and Google Scholar were used to search articles for this study. Results: The findings of this research demonstrate that (1) Que protected the blood‐brain barrier via stimulating Nrf2 in animal stroke, which alleviated ischemic reperfusion and motor dysfunction. (2) By triggering the Nrf2 pathway, Que reduced the neuroinflammation and oxidative damage brought on by TBI in the cortex. (3) In an experimental model of AD, Que enhanced cognitive function by decreasing A1‐4, antioxidant activity, and Nrf2 levels in the brain. Conclusion: We discuss recent research on Que‐mediated Nrf2 expression in the management of several NLDs in this paper.

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“…14 In a different context, the transcription factors ERα, ETS-1, and NRF2 have been related to energy metabolism, mitochondrial biogenesis, and the maintenance of mitochondrial function. [15][16][17] We have also described that Tcf20 is a downstream target of the serine/threonine kinase Akt, 18 which regulates major cellular and tissular functions such as cell growth, liver regeneration and metabolism. 19,20 The previous studies suggest that TCF20 could have several functions beyond those described in neurogenesis, including the regulation of fibrogenesis and mitochondrial metabolism.…”

Section: Key Pointsmentioning

confidence: 99%

“…Also, the protein encoded by TCF20 gene was originally found to regulate the expression of matrix metalloproteinase 3 ( MMP3 ) through its capability to bind to the stromelysin‐1 PDGF‐responsive element (SPRE) in the promoter region of MMP3 gene 14 . In a different context, the transcription factors ERα, ETS‐1, and NRF2 have been related to energy metabolism, mitochondrial biogenesis, and the maintenance of mitochondrial function 15–17 . We have also described that Tcf20 is a downstream target of the serine/threonine kinase Akt, 18 which regulates major cellular and tissular functions such as cell growth, liver regeneration and metabolism 19,20 .…”

Section: Introductionmentioning

confidence: 99%

Tcf20 deficiency is associated with increased liver fibrogenesis and alterations in mitochondrial metabolism in mice and humans

Córdoba-Jover

Ribera

Portolés

et al. 2023

Liver International

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Background & AimsTranscription co‐activator factor 20 (TCF20) is a regulator of transcription factors involved in extracellular matrix remodelling. In addition, TCF20 genomic variants in humans have been associated with impaired intellectual disability. Therefore, we hypothesized that TCF20 has several functions beyond those described in neurogenesis, including the regulation of fibrogenesis.MethodsTcf20 knock‐out (Tcf20−/−) and Tcf20 heterozygous mice were generated by homologous recombination. TCF20 gene genotyping and expression was assessed in patients with pathogenic variants in the TCF20 gene. Neural development was investigated by immufluorescense. Mitochondrial metabolic activity was evaluated with the Seahorse analyser. The proteome analysis was carried out by gas chromatography mass‐spectrometry.ResultsCharacterization of Tcf20−/− newborn mice showed impaired neural development and death after birth. In contrast, heterozygous mice were viable but showed higher CCl4‐induced liver fibrosis and a differential expression of genes involved in extracellular matrix homeostasis compared to wild‐type mice, along with abnormal behavioural patterns compatible with autism‐like phenotypes. Tcf20−/− embryonic livers and mouse embryonic fibroblast (MEF) cells revealed differential expression of structural proteins involved in the mitochondrial oxidative phosphorylation chain, increased rates of mitochondrial metabolic activity and alterations in metabolites of the citric acid cycle. These results parallel to those found in patients with TCF20 pathogenic variants, including alterations of the fibrosis scores (ELF and APRI) and the elevation of succinate concentration in plasma.ConclusionsWe demonstrated a new role of Tcf20 in fibrogenesis and mitochondria metabolism in mice and showed the association of TCF20 deficiency with fibrosis and metabolic biomarkers in humans.

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Activation of the Nrf2 Pathway Prevents Mitochondrial Dysfunction Induced by Caspase-3 Cleaved Tau: Implications for Alzheimer’s Disease

Cited by 16 publications

References 67 publications

Borneol-Modified Schisandrin B Micelles Cross the Blood–Brain Barrier To Treat Alzheimer’s Disease in Aged Mice

Borneol-Modified Schisandrin B Micelles Cross the Blood–Brain Barrier To Treat Alzheimer’s Disease in Aged Mice

Targeting Nrf2 signaling pathway by quercetin in the prevention and treatment of neurological disorders: An overview and update on new developments

Tcf20 deficiency is associated with increased liver fibrogenesis and alterations in mitochondrial metabolism in mice and humans

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