Role of NRF2 in Pathogenesis of Alzheimer’s Disease DOI Creative Commons
Ching‐Tung Chu, Akira Uruno, Fumiki Katsuoka

и другие.

Antioxidants, Год журнала: 2024, Номер 13(12), С. 1529 - 1529

Опубликована: Дек. 13, 2024

Alzheimer’s disease (AD) is a polygenic, multifactorial neurodegenerative disorder and remains the most prevalent form of dementia, globally. Despite decades research efforts, there still no effective cure for this debilitating condition. AD has increasingly focused on transcription factor NRF2 (nuclear erythroid 2-related 2) as potential therapeutic target. plays crucial role in protecting cells tissues from environmental stressors, such electrophiles reactive oxygen species. Recently, an increasing number studies have demonstrated that key regulator pathology. highly expressed microglia, resident macrophages central nervous system, contributes to neuroinflammation, phagocytosis neurodegeneration AD. been reported modulate microglia-induced inflammation facilitate transition homeostatic microglia disease-associated subset. Genetic pharmacological activation improve cognitive function. Here, we review current understanding involvement critical context Our aim highlight targeting promising strategy mitigating progression

Язык: Английский

Synaptic plasticity and neuroprotection: The molecular impact of flavonoids on neurodegenerative disease progression DOI

Spandana Rajendra Kopalli,

Tapan Behl,

Ashishkumar Kyada

и другие.

Neuroscience, Год журнала: 2025, Номер 569, С. 161 - 183

Опубликована: Фев. 7, 2025

Язык: Английский

Процитировано

1
Resveratrol-Enhanced Human Neural Stem Cell-Derived Exosomes Mitigate MPP+-Induced Neurotoxicity Through Activation of AMPK and Nrf2 Pathways and Inhibition of the NLRP3 Inflammasome in SH-SY5Y Cells DOI Creative Commons
Tony F. Chan, Yuping Yang, Christopher J.B. Nicol

и другие.

Life, Год журнала: 2025, Номер 15(2), С. 294 - 294

Опубликована: Фев. 13, 2025

Parkinson's disease (PD) is a progressive neurodegenerative disorder primarily characterized by the loss of dopaminergic neurons in substantia nigra. Mitochondrial dysfunction, oxidative stress, and neuroinflammation are recognized as critical pathological mechanisms driving neurodegeneration PD. Exosome (Exo)-based therapies, particularly those derived from human neural stem cells (hNSCs), offer promising neuroprotective effects due to their ability transfer bioactive molecules that modulate cellular processes. Resveratrol (RES), polyphenolic compound with potent antioxidant anti-inflammatory properties, has been shown enhance therapeutic potential cell (SC)-derived Exos. This study investigated RES-treated hNSCs-derived Exos (RES-hNSCs-Exos) on SH-SY5Y exposed 1-methyl-4-phenylpyridinium (MPP+), neurotoxin commonly used model Parkinsonian neurotoxicity. Treating MPP+ led significant reductions viability, mitochondrial increased activation inflammatory pathways. Treatment RES-hNSCs-Exos rescued MPP+-induced toxicity improving enhancing ATP production, increasing biogenesis, reducing reactive oxygen species (ROS) generation. The findings also demonstrated expression essential genes involved such PGC1α, NRF1, Tfam, indicating improved function presence RES-hNSCs-Exos. Further analysis revealed these protective were mediated activating AMP-activated protein kinase (AMPK) Nrf2 signaling pathways, which promoted health reduced stress. Moreover, treatment suppressed downregulating NLRP3 inflammasome secretion pro-inflammatory cytokines IL-1β IL-18. In conclusion, results suggest exhibit against neurotoxicity function, inhibiting neuroinflammation. These highlight hNSCs-Exos novel strategy for diseases like PD, RES valuable enhancer efficacy.

Язык: Английский

Процитировано

1
Nrf2/Bach1 signaling axis: A promising multifaceted therapeutic strategy for Alzheimer's disease DOI Creative Commons

Priyanka Soni,

Sudarshana M. Sharma, Andrew A. Pieper

и другие.

Neurotherapeutics, Год журнала: 2025, Номер unknown, С. e00586 - e00586

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

1
Protein sequence editing defines distinct and overlapping functions of SKN-1A/Nrf1 and SKN-1C/Nrf2. DOI Creative Commons

Briar E. Jochim,

Irini Topalidou, Nicolas J. Lehrbach

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

ABSTRACT The Nrf/NFE2L family of transcription factors regulates redox balance, xenobiotic detoxification, metabolism, proteostasis, and aging. Nrf1/NFE2L1 is primarily responsible for stress-responsive upregulation proteasome subunit genes essential adaptation to proteotoxic stress. Nrf2/NFE2L2 mainly involved in activating oxidative stress responses promoting detoxification. Nrf1 Nrf2 contain very similar DNA binding domains can drive transcriptional responses. In C. elegans , a single gene, skn-1 encodes distinct protein isoforms, SKN-1A SKN-1C, that function analogously mammalian Nrf2, respectively, share an identical domain. Thus, the extent which SKN-1A/Nrf1 SKN-1C/Nrf2 functions are or overlapping has been unclear. Regulation by requires post-translational conversion N-glycosylated asparagine residues aspartate PNG-1/NGLY1 peptide:N-glycanase, process we term ‘sequence editing’. Here, reveal consequences sequence editing transcriptomic output activated SKN-1A. We confirm activation strictly dependent on editing. addition, find edited also activate linked homeostasis detoxification regulated but these genes’ antagonized Using mutant alleles selectively inactivate either show both isoforms promote optimal resistance, acting as effectors signaling pathways. These findings suggest governs SKN-1/Nrf tuning transcriptome.

Язык: Английский

Процитировано

0
Oxidative Stress and Redox Imbalance: Common Mechanisms in Cancer Stem Cells and Neurodegenerative Diseases DOI Creative Commons

Nikhil Raj Selvaraj,

Durga Nandan,

B J Bipin Nair

и другие.

Cells, Год журнала: 2025, Номер 14(7), С. 511 - 511

Опубликована: Март 29, 2025

Oxidative stress (OS) is an established hallmark of cancer and neurodegenerative disorders (NDDs), which contributes to genomic instability neuronal loss. This review explores the contrasting role OS in stem cells (CSCs) NDDs. Elevated levels reactive oxygen species (ROS) contribute promote tumor initiation progression CSCs, while NDDs such as Alzheimer’s Parkinson’s disease, accelerates death impairs cellular repair mechanisms. Both scenarios involve disruption delicate balance between pro-oxidant antioxidant systems, leads chronic oxidative stress. Notably, CSCs neurons display alterations redox-sensitive signaling pathways, including Nrf2 NF-κB, influence cell survival, proliferation, differentiation. Mitochondrial dynamics further illustrate these differences: enhanced function supports adaptability whereas impairments heighten vulnerability. Understanding common mechanisms OS-induced redox imbalance may provide insights for developing interventions, addressing aging hallmarks, potentially mitigating or preventing both

Язык: Английский

Процитировано

0
Integrated Computational and Experimental Approach to Identify Nrf2-Regulated Molecular Targets in Cerebral Ischemia DOI

Anita Lewczuk,

Anna Boratyńska-Jasińska,

Łukasz Charzewski

и другие.

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
The Underestimated Role of Iron in Frontotemporal Dementia: A Narrative Review DOI Open Access

Sara Ferretti,

Isabella Zanella

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 12987 - 12987

Опубликована: Дек. 3, 2024

The term frontotemporal dementia (FTD) comprises a group of neurodegenerative disorders characterized by the progressive degeneration frontal and temporal lobes brain with language impairment changes in cognitive, behavioral executive functions, some cases motor manifestations. A high proportion FTD are due to genetic mutations inherited an autosomal-dominant manner variable penetrance depending on implicated gene. Iron is crucial microelement that involved several cellular essential functions whole body plays additional specialized roles central nervous system (CNS) mainly through its redox-cycling properties. Such feature may be harmful under aerobic conditions, since it lead generation highly reactive hydroxyl radicals. Dysfunctions iron homeostasis CNS indeed disorders, although still challenging determine whether dyshomeostasis this but metal direct cause neurodegeneration, contributor factor or simply consequence other mechanisms. Unlike many evidence dysfunction scarce; nonetheless, recent literature intriguingly suggests possible involvement. present review aims summarize what currently known about contribution based clinical, imaging, histological, biochemical molecular studies, further suggesting new perspectives offering insights for future investigations underexplored field research.

Язык: Английский

Процитировано

0
Centella asiatica Promotes Antioxidant Gene Expression and Mitochondrial Oxidative Respiration in Experimental Autoimmune Encephalomyelitis DOI Creative Commons

Payel Kundu,

Kanon Yasuhara,

Mikah S. Brandes

и другие.

Pharmaceuticals, Год журнала: 2024, Номер 17(12), С. 1681 - 1681

Опубликована: Дек. 13, 2024

Background/Objectives: Centella asiatica (L.) Urban (family Apiaceae) (C. asiatica) is a traditional botanical medicine used in aging and dementia. Water extracts of C. (CAW) have been to treat neuropsychiatric symptoms related animal models are associated with increases antioxidant response element (ARE) genes improvements mitochondrial respiratory function neuronal health. Because multiple sclerosis (MS) shares its neurogenerative pathology oxidative stress dysfunction dementia, MS may also benefit from asiatica. To determine whether CAW similarly benefits symptoms, ARE gene expression, respiration inflammatory MS, the effects on clinical disability inflammation, we tested using experimental autoimmune encephalomyelitis (EAE). Methods: C57BL/6J mice induced EAE were treated or placebo for 2 weeks. The outcomes disability, signs anxiety (open field test), respiration, inflammation demyelination. Results: At dosing schedule concentrations tested, CAW-treated demonstrated increased expression activity compared those placebo-treated EAE. was reduced infiltrates spinal cord, but differences between populations activated versus quiescent microglia equivocal. did not improve behavioral performance, motor Conclusions: In model demonstrates similar neuroprotective it exhibits dementia mouse models. These benefits, along anti-inflammatory CAW, support further investigation people MS.

Язык: Английский

Процитировано

0
Role of NRF2 in Pathogenesis of Alzheimer’s Disease DOI Creative Commons
Ching‐Tung Chu, Akira Uruno, Fumiki Katsuoka

и другие.

Antioxidants, Год журнала: 2024, Номер 13(12), С. 1529 - 1529

Опубликована: Дек. 13, 2024

Alzheimer’s disease (AD) is a polygenic, multifactorial neurodegenerative disorder and remains the most prevalent form of dementia, globally. Despite decades research efforts, there still no effective cure for this debilitating condition. AD has increasingly focused on transcription factor NRF2 (nuclear erythroid 2-related 2) as potential therapeutic target. plays crucial role in protecting cells tissues from environmental stressors, such electrophiles reactive oxygen species. Recently, an increasing number studies have demonstrated that key regulator pathology. highly expressed microglia, resident macrophages central nervous system, contributes to neuroinflammation, phagocytosis neurodegeneration AD. been reported modulate microglia-induced inflammation facilitate transition homeostatic microglia disease-associated subset. Genetic pharmacological activation improve cognitive function. Here, we review current understanding involvement critical context Our aim highlight targeting promising strategy mitigating progression

Язык: Английский

Процитировано

0