The Role of NRF2 in Cerebrovascular Protection: Implications for Vascular Cognitive Impairment and Dementia (VCID)

Hu, Yizhou; Zhang, Feng; Ikonomovic, Milos; Yang, Tuo

doi:10.3390/ijms25073833

IJMS

2024

DOI: 10.3390/ijms25073833

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The Role of NRF2 in Cerebrovascular Protection: Implications for Vascular Cognitive Impairment and Dementia (VCID)

Yizhou Hu,

Feng Zhang,

Milos Ikonomovic

et al.

Abstract: Vascular cognitive impairment and dementia (VCID) represents a broad spectrum of cognitive decline secondary to cerebral vascular aging and injury. It is the second most common type of dementia, and the prevalence continues to increase. Nuclear factor erythroid 2-related factor 2 (NRF2) is enriched in the cerebral vasculature and has diverse roles in metabolic balance, mitochondrial stabilization, redox balance, and anti-inflammation. In this review, we first briefly introduce cerebrovascular aging in VCID and… Show more

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Cited by 2 publications

References 238 publications

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Role of NRF2 in Pathogenesis of Alzheimer’s Disease

Chu,

Uruno,

Katsuoka

et al. 2024

Antioxidants

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

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Role of NRF2 in Pathogenesis of Alzheimer’s Disease

Chu,

Uruno,

Katsuoka

et al. 2024

Antioxidants

View full text Add to dashboard Cite

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Characterization of Proteome Changes in Aged and Collagen VI-Deficient Human Pericyte Cultures

Moriggi,

Torretta,

Cescon

et al. 2024

IJMS

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Pericytes are a distinct type of cells interacting with endothelial cells in blood vessels and contributing to endothelial barrier integrity. Furthermore, pericytes show mesenchymal stem cell properties. Muscle-derived pericytes can demonstrate both angiogenic and myogenic capabilities. It is well known that regenerative abilities and muscle stem cell potential decline during aging, leading to sarcopenia. Therefore, this study aimed to investigate the potential of pericytes in supporting muscle differentiation and angiogenesis in elderly individuals and in patients affected by Ullrich congenital muscular dystrophy or by Bethlem myopathy, two inherited conditions caused by mutations in collagen VI genes and sharing similarities with the progressive skeletal muscle changes observed during aging. The study characterized pericytes from different age groups and from individuals with collagen VI deficiency by mass spectrometry-based proteomic and bioinformatic analyses. The findings revealed that aged pericytes display metabolic changes comparable to those seen in aging skeletal muscle, as well as a decline in their stem potential, reduced protein synthesis, and alterations in focal adhesion and contractility, pointing to a decrease in their ability to form blood vessels. Strikingly, pericytes from young patients with collagen VI deficiency showed similar characteristics to aged pericytes, but were found to still handle oxidative stress effectively together with an enhanced angiogenic capacity.

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The Role of NRF2 in Cerebrovascular Protection: Implications for Vascular Cognitive Impairment and Dementia (VCID)

Cited by 2 publications

References 238 publications

Role of NRF2 in Pathogenesis of Alzheimer’s Disease

Role of NRF2 in Pathogenesis of Alzheimer’s Disease

Characterization of Proteome Changes in Aged and Collagen VI-Deficient Human Pericyte Cultures

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