Drug repurposing on Alzheimer's disease through modulation of NRF2 neighborhood

Bourdakou, Marilena M.; Fernández-Ginés, Raquel; Cuadrado, Antonio; Spyrou, George M.

doi:10.1016/j.redox.2023.102881

Cited by 6 publications

(2 citation statements)

References 68 publications

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“…NRF2 activators have been extensively studied in preclinical settings; however, which compounds to proceed with in VCID clinical trials is hard to determine. Five candidate compounds (curcumin, trichostatin-a, panobinostat, parthenolide, and entinostat) have been identified for AD treatment based on structural similarities, NRF2-diseasome, targeted pathways, and modes [237]. A selected list of NRF2 activators that are currently being trialed in CNS diseases is listed in Table 1.…”

Section: Future Perspectives On Nrf2 In Vcidmentioning

confidence: 99%

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

Hu,

Zhang,

Ikonomovic

et al. 2024

IJMS

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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 the NRF2 pathway. We then extensively discuss the effects of NRF2 activation in cerebrovascular components such as endothelial cells, vascular smooth muscle cells, pericytes, and perivascular macrophages. Finally, we summarize the clinical potential of NRF2 activators in VCID.

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Section: Future Perspectives On Nrf2 In Vcidmentioning

confidence: 99%

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

Hu,

Zhang,

Ikonomovic

et al. 2024

IJMS

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“…Indeed, excessive oxidative stress levels are correlated with neuronal apoptosis and abnormal cerebral functioning, as demonstrated in individuals diagnosed with middle to advanced AD stages. , Consequently, the manipulation of damaged cell function from an upstream perspective represents a novel therapeutic approach with significant implications for long-term AD treatment. , Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) plays a pivotal role in maintaining cellular redox homeostasis and remains inactive under normal conditions. ,, Upon exposure to external oxidative stress, Nrf2 is activated and translocated to the nucleus, triggering the transcription of downstream antioxidant proteins that safeguard cells against oxidative damage. However, persistent overactivation of Nrf2 can facilitate tumorigenesis by reprogramming a wide range of cancer metabolic pathways. , Hence, precise modulation of Nrf2-mediated signaling holds promise for long-term therapeutic intervention in AD. ,, …”

mentioning

confidence: 99%

A Nanozyme-Boosted MOF-CRISPR Platform for Treatment of Alzheimer’s Disease

Yang,

Qin,

Liu

et al. 2024

Nano Lett.

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Rectifying the aberrant microenvironment of a disease through maintenance of redox homeostasis has emerged as a promising perspective with significant therapeutic potential for Alzheimer's disease (AD). Herein, we design and construct a novel nanozyme-boosted MOF-CRISPR platform (CMOPKP), which can maintain redox homeostasis and rescue the impaired microenvironment of AD. By modifying the targeted peptides KLVFFAED, CMOPKP can traverse the blood−brain barrier and deliver the CRISPR activation system for precise activation of the Nrf2 signaling pathway and downstream redox proteins in regions characterized by oxidative stress, thereby reinstating neuronal antioxidant capacity and preserving redox homeostasis. Furthermore, cerium dioxide possessing catalase enzyme-like activity can synergistically alleviate oxidative stress. Further in vivo studies demonstrate that CMOPKP can effectively alleviate cognitive impairment in 3xTg-AD mouse models. Therefore, our design presents an effective way for regulating redox homeostasis in AD, which shows promise as a therapeutic strategy for mitigating oxidative stress in AD.

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Review on pathogenesis and treatment of Alzheimer's disease

Cai,

Liu,

Fan

2024

Developmental Dynamics

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The rising incidence of Alzheimer's disease (AD) and the associated economic impacts has prompted a global focus in the field. In recent years, there has been a growing understanding of the pathogenic mechanisms of AD, including the aggregation of β‐amyloid, hyperphosphorylated tau, and neuroinflammation. These processes collectively lead to neurodegeneration and cognitive decline, which ultimately results in the loss of autonomy in patients. Currently, there are three main types of AD treatments: clinical tools, pharmacological treatment, and material interventions. This review provides a comprehensive analysis of the underlying etiology and pathogenesis of AD, as well as an overview of the current prevalence of AD treatments. We believe this article can help deepen our understanding of the AD mechanism, and facilitate the clinical translation of scientific research or therapies, to address this global problem of AD.

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Drug repurposing on Alzheimer's disease through modulation of NRF2 neighborhood

Cited by 6 publications

References 68 publications

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

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

A Nanozyme-Boosted MOF-CRISPR Platform for Treatment of Alzheimer’s Disease

Review on pathogenesis and treatment of Alzheimer's disease

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