Nrf2 pathways in neuroprotection: Alleviating mitochondrial dysfunction and cognitive impairment in aging

Life Sciences, Год журнала: 2024, Номер 357, С. 123056 - 123056

Опубликована: Сен. 12, 2024

Язык: Английский

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The role of NURR1 in metabolic abnormalities of Parkinson’s disease

Molecular Neurodegeneration, Год журнала: 2022, Номер 17(1)

Опубликована: Июнь 27, 2022

A constant metabolism and energy supply are crucial to all organs, particularly the brain. Age-dependent neurodegenerative diseases, such as Parkinson's disease (PD), associated with alterations in cellular metabolism. These changes have been recognized a novel hot topic that may provide new insights help identify risk pre-symptomatic phase of disease, understand pathogenesis, track progression, determine critical endpoints. Nuclear receptor-related factor 1 (NURR1), an orphan member nuclear receptor superfamily transcription factors, is major pathogenesis PD, NURR1 expression can detrimental effect on In this review, we discuss recent evidence suggests vital role dopaminergic (DAergic) neuron development PD. The association between metabolic abnormalities its implications for PD therapy further highlighted.

Язык: Английский

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Aging Effects on Optic Nerve Neurodegeneration

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2573 - 2573

Опубликована: Янв. 29, 2023

Common risk factors for many ocular pathologies involve non-pathologic, age-related damage to the optic nerve. Understanding mechanisms of changes can facilitate targeted treatments that arise at any point in life. In this review, we examine these age-related, neurodegenerative nerve, contextualize from anatomic molecular level, and appreciate their relationship with pathophysiology. From simple structural mechanical nerve head (ONH), epigenetic biochemical alterations tissue environment, multiple age-dependent drive extracellular matrix (ECM) remodeling, retinal ganglion cell (RGC) loss, lowered regenerative ability respective axons. conjunction, aging decreases myelin preserve maximal conductivity, even “successfully” regenerated Glial cells, however, regeneratively overcompensate result a microenvironment promotes RGC axonal death. Better elucidating neurodegeneration remains interest, specifically investigating human ECM, RGCs, axons, oligodendrocytes, astrocytes; clarifying exact processes aged connective ultrastructural impacts; developing novel technologies pharmacotherapies target known genetic, biochemical, matrisome, neuroinflammatory markers. Management models should account when addressing glaucoma, diabetic retinopathy, other blinding diseases.

Язык: Английский

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Protective roles of peroxiporins AQP0 and AQP11 in human astrocyte and neuronal cell lines in response to oxidative and inflammatory stressors

Bioscience Reports, Год журнала: 2024, Номер 44(3)

Опубликована: Март 1, 2024

Abstract In addition to aquaporin (AQP) classes AQP1, AQP4 and AQP9 known be expressed in mammalian brain, our recent transcriptomic analyses identified AQP0 AQP11 human cortex hippocampus at levels correlated with age Alzheimer’s disease (AD) status; however, protein localization remained unknown. Roles of transporting hydrogen peroxide (H2O2) lens kidney prompted hypothesis that up-regulation brain might similarly protective. Established cell lines for astroglia (1321N1) neurons (SHSY5Y, differentiated retinoic acid) were used monitor changes transcript AQPs (AQP0 AQP12) response inflammation (simulated 10–100 ng/ml lipopolysaccharide [LPS], 24 h), hypoxia (5 min N2, followed by 0 h normoxia). AQP transcripts up-regulated both 1321N1 SHSY5Y included AQP0, AQP1 AQP11. Immunocytochemistry cells confirmed expression plasma membrane endoplasmic reticulum; increased 10-fold after LPS 0.3-fold. cells, 0.2-fold LPS; showed no appreciable change. Proposed peroxiporin roles tested using melondialdehyde (MDA) assays quantify lipid peroxidation brief H2O2. Boosting pretreatment lowered subsequent H2O2-induced MDA responses (∼50%) compared controls; conversely small interfering RNA knockdown (∼17%) H2O2, a similar trend siRNA. Interventions increase native activity are promising as new approaches mitigate damage caused aging neurodegeneration.

Язык: Английский

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The Neuroprotective Flavonoids Sterubin and Fisetin Maintain Mitochondrial Health under Oxytotic/Ferroptotic Stress and Improve Bioenergetic Efficiency in HT22 Neuronal Cells

Antioxidants, Год журнала: 2024, Номер 13(4), С. 460 - 460

Опубликована: Апрель 13, 2024

The global increase in the aging population has led to a rise many age-related diseases with continuing unmet therapeutic needs. Research into molecular mechanisms underlying both and neurodegeneration identified promising targets, such as oxytosis/ferroptosis cell death pathway, which mitochondrial dysfunction plays critical role. This study focused on sterubin fisetin, two flavonoids from natural pharmacopeia previously strong inhibitors of pathway. Here, we investigated effects compounds physiology HT22 hippocampal nerve cells under oxytotic/ferroptotic stress. We show that can restore homeostasis at level redox regulation, calcium uptake, biogenesis, fusion/fission dynamics, modulation respiration, leading enhancement bioenergetic efficiency. However, mitochondria are not required for neuroprotective highlighting their diverse homeostatic impacts. Sterubin thus, provide opportunities expand drug development strategies anti-oxytotic/ferroptotic agents offer new perspectives intricate interplay between function, cellular stress, pathophysiology neurodegenerative disorders.

Язык: Английский

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Recent advances in fluorescent probes for ATP imaging

Talanta, Год журнала: 2024, Номер 279, С. 126622 - 126622

Опубликована: Июль 28, 2024

Язык: Английский

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Glucose transporter 3 in neuronal glucose metabolism: Health and diseases

Metabolism, Год журнала: 2021, Номер 123, С. 154869 - 154869

Опубликована: Авг. 21, 2021

Язык: Английский

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Characteristics of Neural Network Changes in Normal Aging and Early Dementia

Frontiers in Aging Neuroscience, Год журнала: 2021, Номер 13

Опубликована: Ноя. 22, 2021

To understand the mechanisms underlying preserved and impaired cognitive function in healthy aging dementia, respectively, spatial relationships of brain networks their resilience should be understood. The hub regions brain, such as multisensory integration default mode networks, are critical for within- between-network communication, remain well-preserved during aging, play an essential role compensatory processes. On other hand, these hubs preferred sites lesions neurodegenerative dementias, Alzheimer’s disease. Disrupted primary information processing auditory, visual, sensorimotor may lead to overactivity accumulation pathological proteins that cause dementia. At cellular level, contain many synapses require a large amount energy. These rich ATP-related gene expression had high glucose metabolism demonstrated on positron emission tomography (PET). Importantly, number mitochondria, which center ATP production, decline by about 8% every 10 years. Dementia patients often have dysfunction ubiquitin-proteasome autophagy-lysosome systems, amounts ATP. If there is low energy supply but demand high, risk disease can high. Imbalance between important development This imbalance explain why vulnerable damage different dementias. Here, we review (1) characteristics gray matter network, white resting state functional network changes related (2) disruption (3) associated with disruption.

Язык: Английский

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Nurr1 Modulation Mediates Neuroprotective Effects of Statins

Advanced Science, Год журнала: 2022, Номер 9(18)

Опубликована: Апрель 30, 2022

Abstract The ligand‐sensing transcription factor Nurr1 emerges as a promising therapeutic target for neurodegenerative pathologies but ligands functional studies and validation are lacking. Here pronounced modulation by statins which clinically relevant neuroprotective effects demonstrated, is reported. Several directly affect activity in cellular cell‐free settings with low micromolar to sub‐micromolar potencies. Simvastatin example exhibits anti‐inflammatory astrocytes, abrogated knockdown. Differential gene expression analysis native Nurr1‐silenced cells reveals strong proinflammatory of knockdown while simvastatin treatment induces several mechanisms via involving changes inflammatory, metabolic cell cycle expression. Further vitro evaluation confirms reduced inflammatory response, improved glucose metabolism, inhibition simvastatin‐treated neuronal cells. These findings suggest involvement the well‐documented mechanistically elusive neuroprotection statins.

Язык: Английский

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Omics data integration suggests a potential idiopathic Parkinson’s disease signature

Communications Biology, Год журнала: 2023, Номер 6(1)

Опубликована: Ноя. 20, 2023

The vast majority of Parkinson's disease cases are idiopathic. Unclear etiology and multifactorial nature complicate the comprehension pathogenesis. Identification early transcriptomic metabolic alterations consistent across different idiopathic (IPD) patients might reveal potential basis increased dopaminergic neuron vulnerability primary mechanisms. In this study, we combine systems biology data integration approaches to identify differences in signatures between IPD patient healthy individual-derived midbrain neural precursor cells. Characterization gene expression modeling pyruvate, several amino acid lipid metabolism as most dysregulated pathways precursors. Furthermore, show that precursors endure mitochondrial impairment a reduced total NAD pool. Accordingly, treatment with increases ATP yield hence demonstrating rescue IPD-associated changes.

Язык: Английский

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