Vitamin K2 protects against Aβ42-induced neurotoxicity by activating autophagy and improving mitochondrial function in Drosophila

Lin, Xiaohui; Wen, Xin; Wei, Zaiwa; Guo, Keyi; Shi, Fang; Huang, Tingting; Wang, Wenjing; Zheng, Jinou

doi:10.1097/wnr.0000000000001599

Cited by 22 publications

(14 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In accordance with the present study, a recent report showed that vitamin K2 along with inhibition of Nauk1 attenuated sevoflurane-induced tau phosphorylation and cognitive impairment in neonatal mice [68]. Vitamin K2 was also found to be effective against Aβ42-induced toxicity and increased ATP production in Alzheimer's disease Drosophila [53]. In case of AD, activation of p38 MAPK is linked to phosphorylation of tau and the formation of tau tangles leading to apoptosis [69].…”

Section: Discussionsupporting

confidence: 90%

“…Thus, vitamin K2 played an important role in preserving mitochondrial function and thus, prevented the activation of mitochondrial dysfunction-related neuronal cell death. Protection of mitochondrial function by vitamin K2 is also supported by a recent report where vitamin K2 was found to increase ATP production and increase the expression of autophagy-related genes in the AD model of Drosophila [53]. Moreover, it was observed that vitamin K2 (MK-7) increases ATP levels in patients with Parkinson's disease and mitochondrial dysfunction [54].…”

Section: Discussionmentioning

confidence: 57%

See 1 more Smart Citation

Vitamin K2 Modulates Organelle Damage and Tauopathy Induced by Streptozotocin and Menadione in SH-SY5Y Cells

2021

View full text Add to dashboard Cite

Vitamin K2, known for its antioxidative and anti-inflammatory properties, can act as a potent neuroprotective molecule. Despite its action against mitochondrial dysfunction, the mechanism underlying the links between the protective effects of vitamin K2 and endoplasmic reticulum (ER) stress along with basal levels of total tau protein and amyloid-beta 42 (Aβ42) has not been elucidated yet. To understand the neuroprotective effect of vitamin K2 during metabolic complications, SH-SY5Y cells were treated with streptozotocin for 24 h and menadione for 2 h in a dose-dependent manner, followed by post-treatment of vitamin K2 for 5 h. The modulating effects of vitamin K2 on cell viability, lactate dehydrogenase release, reactive oxygen species (ROS), mitochondrial membrane potential, ER stress marker (CHOP), an indicator of unfolded protein response (UPR), inositol requiring enzyme 1 (p-IRE1α), glycogen synthase kinase 3 (GSK3α/β), total tau and Aβ42 were studied. Results showed that vitamin K2 significantly reduces neuronal cell death by inhibiting cytotoxicity and ROS levels and helps in the retainment of mitochondrial membrane potential. Moreover, vitamin K2 significantly decreased the expression of CHOP protein along with the levels and the nuclear localization of p-IRE1 α, thus showing its significant role in inhibiting chronic ER stress-mediated UPR and eventually cell death. In addition, vitamin K2 significantly down-regulated the expression of GSK3 α/β together with the levels of total tau protein, with a petite effect on secreted Aβ42 levels. These results suggested that vitamin K2 alleviated mitochondrial damage, ER stress and tauopathy-mediated neuronal cell death, which highlights its role as new antioxidative therapeutics targeting related cellular processes.

show abstract

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 57%

Vitamin K2 Modulates Organelle Damage and Tauopathy Induced by Streptozotocin and Menadione in SH-SY5Y Cells

2021

View full text Add to dashboard Cite

show abstract

“…Like negative geotaxis assays, RING assays can be used for both genetic screens and screening compounds for therapeutic value (Liu et al, 2015 ). The study conducted by Lin et al ( 2021 ) found Vitamin K2 to improve climbing ability measured by RING assay in a D. melanogaster model of AD (Lin et al, 2021 ).…”

Section: The Therapeutic Potential Of Using D Melanogaster ...mentioning

confidence: 99%

Animal Models of Neurodegenerative Disease: Recent Advances in Fly Highlight Innovative Approaches to Drug Discovery

Tello

Williams

Eppler

et al. 2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Neurodegenerative diseases represent a formidable challenge to global health. As advances in other areas of medicine grant healthy living into later decades of life, aging diseases such as Alzheimer's disease (AD) and other neurodegenerative disorders can diminish the quality of these additional years, owed largely to the lack of efficacious treatments and the absence of durable cures. Alzheimer's disease prevalence is predicted to more than double in the next 30 years, affecting nearly 15 million Americans, with AD-associated costs exceeding $1 billion by 2050. Delaying onset of AD and other neurodegenerative diseases is critical to improving the quality of life for patients and reducing the burden of disease on caregivers and healthcare systems. Significant progress has been made to model disease pathogenesis and identify points of therapeutic intervention. While some researchers have contributed to our understanding of the proteins and pathways that drive biological dysfunction in disease using in vitro and in vivo models, others have provided mathematical, biophysical, and computational technologies to identify potential therapeutic compounds using in silico modeling. The most exciting phase of the drug discovery process is now: by applying a target-directed approach that leverages the strengths of multiple techniques and validates lead hits using Drosophila as an animal model of disease, we are on the fast-track to identifying novel therapeutics to restore health to those impacted by neurodegenerative disease.

show abstract

“…AD, leading to loss of memory and cognitive function, is reported to occur due to Amyloid-β (Aβ) accumulation and neural cell death. Number of studies demonstrated the protective role of vitamin K2 in inhibiting Aβ cytotoxicity, caspase-3 induced apoptosis and by rescuing mitochondrial dysfunction [75,76]. However, to potentiate the anti-Alzheimer's and anti-Parkinson's role of VK2, more elaborate human trials/intervention studies are needed.…”

Section: Cognition and Brain Healthmentioning

confidence: 99%

Vitamin K2: An emerging essential nutraceutical and its market potential

Sunita¹,

Gupta²,

S³

et al. 2022

J Appl Biol Biotech

View full text Add to dashboard Cite

Vitamin K has recently gained importance as a potential therapeutic agent beyond blood coagulation. Vitamin K2 is found to be a superior nutrient supplement than K1. K1 is mainly obtained from leafy vegetables, whereas K2 is sourced from fermented products and gut microbiota. However, in contrast to other fat-soluble vitamins, body does not accumulate vitamin K and depends on K cycle for its effective use. Vitamin K2 regulates body calcium metabolism. An insufficient vitamin K2 dose increases the risk of osteoporosis, bone fractures, and cardiovascular diseases. Despite a lot of available literature and also approval by safety regulatory bodies, including Food and Drug Administratio (FDA), its awareness among healthcare professionals and general public is still poor. This understudied nutrient has gained a lot of attention in the market because of its multifaceted role in disease management. Aggressive competition within key sellers is one of the critical factors, which expeditiously upsurge the market growth of vitamin K. The rapid increase in patent applications during the last decade reflects its worldwide recognition as an emerging nutraceutical and hence its future market potential.

show abstract

Vitamin K2 protects against Aβ42-induced neurotoxicity by activating autophagy and improving mitochondrial function in Drosophila

Abstract: Supplemental Digital Content is available in the text.

Cited by 22 publications

References 30 publications

Vitamin K2 Modulates Organelle Damage and Tauopathy Induced by Streptozotocin and Menadione in SH-SY5Y Cells

Vitamin K2 Modulates Organelle Damage and Tauopathy Induced by Streptozotocin and Menadione in SH-SY5Y Cells

Animal Models of Neurodegenerative Disease: Recent Advances in Fly Highlight Innovative Approaches to Drug Discovery

Vitamin K2: An emerging essential nutraceutical and its market potential

Contact Info

Product

Resources

About