Aging, NRF2, and TAU: A Perfect Match for Neurodegeneration?

Antioxidants, Journal Year: 2023, Volume and Issue: 12(8), P. 1564 - 1564

Published: Aug. 4, 2023

Although the trigger for neurodegenerative disease process is unknown, relevance of aging stands out as a major risk development neurodegeneration. In this review, we highlighted relationship between different cellular mechanisms that occur consequence and transcription factor nuclear erythroid-2-related 2 (NRF2) connection with TAU protein. We focused on NRF2 in main processes involved neurodegeneration associated aging, such genomic instability, protein degradation systems (proteasomes/autophagy), senescence, stem cell exhaustion, well inflammation. also analyzed effect levels its aggregation spread process. Finally, investigated interconnection alterations signaling pathway both primary secondary tauopathies. All these points highlight possible therapeutic target

Language: Английский

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Unlocking the therapeutic potential of natural stilbene: Exploring pterostilbene as a powerful ally against aging and cognitive decline

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 92, P. 102125 - 102125

Published: Nov. 17, 2023

Language: Английский

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Slingshot homolog-1–mediated Nrf2 sequestration tips the balance from neuroprotection to neurodegeneration in Alzheimer’s disease

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(30)

Published: July 18, 2023

Oxidative damage in the brain is one of earliest drivers pathology Alzheimer’s disease (AD) and related dementias, both preceding exacerbating clinical symptoms. In response to oxidative stress, nuclear factor erythroid 2-related 2 (Nrf2) normally activated protect from damage. However, Nrf2-mediated defense against stress declines AD, rendering increasingly vulnerable Although this phenomenon has long been recognized, its mechanistic basis a mystery. Here, we demonstrate through vitro vivo models, as well human AD tissue, that Slingshot homolog-1 (SSH1) drives effect by acting counterweight neuroprotective Nrf2 disease. Specifically, stress-activated SSH1 suppresses signaling sequestering complexes on actin filaments augmenting Kelch-like ECH-associated protein 1 (Keap1)–Nrf2 interaction, independently phosphatase activity. We also show Ssh1 elimination models increases activation, which mitigates tau amyloid-β accumulation protects injury, neuroinflammation, neurodegeneration. Furthermore, loss preserves normal synaptic function transcriptomic patterns P301S mice. Importantly, brains exhibit highly elevated interactions with Keap1. Thus, here unique mode blockade occurs SSH1, ensuing pathogenesis AD. Strategies inhibit SSH1-mediated suppression while preserving catalytic may provide new therapies for dementias.

Language: Английский

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Redox Metabolism and Autonomic Regulation During Aging: Can Heart Rate Variability Be Used to Monitor Healthy Longevity?

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 161 - 161

Published: Jan. 10, 2025

The functionality of redox metabolism is frequently named as an important contributor to the processes aging and anti-aging. Excessive activation free radical reactions accompanied by inability antioxidant defense (AOD) mechanisms control flow reactive oxygen species (ROS) leads persistence oxidative stress, hypoxia, impaired mitochondrial energy function reduced ATP potential. From a long-term perspective, such changes contribute development chronic diseases facilitate aging. In turn, preconditioning biosystem with small doses stressful stimuli might cause mobilization AOD excessive ROS, which supports optimal functioning reactions. Those are crucial importance for anti-aging also known eustress or hormetic response. To ensure continuous support mild pro-oxidant activity in metabolic system, close monitoring timely corrections preventing ROS production required. paper introduces potential heart rate variability (HRV) biomarker functional reserves tool measure stress resilience during practical approaches interpretation HRV provided based on total power, power response orthostatic test activities all spectral components. It suggested that complex those parameters can reflect depth may be used guide lifestyle interventions promote active longevity.

Language: Английский

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Nicotinamide riboside alleviates sweeteners-induced brain and cognitive impairments in immature mice

Food & Function, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Nicotinamide riboside alleviated cognitive impairment induced by sucrose/aspartame, which might be related to neuroinflammation, pyroptosis, oxidative stress, apoptosis and autophagy.

Language: Английский

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