Role of Neural Stem Cells and Vitamin D Receptor (VDR)–Mediated Cellular Signaling in the Mitigation of Neurological Diseases

Uthaiah, Chinnappa A.; Beeraka, Narasimha M; Ramashetty, Rajalakshmi; Ramya, C. M.; Madhunapantula, SubbaRao V.

doi:10.1007/s12035-022-02837-z

Cited by 11 publications

(5 citation statements)

References 320 publications

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“…This finding has sparked further research into the anti-senescence effects of VDR, which has been demonstrated to reduce senescence phenotypes in neural stem cells, epithelial cells of the skin, muscle cells, and more. 54,71,74 Our experiments have confirmed this anti-senescence effect by showing that VDR signaling not only was reduced during BMSC senescence under high-fat conditions but also helped BMSCs resist senescence both in vitro and in vivo. The ability of increased VDR to rescue BMSC senescence in a high-fat microenvironment suggests that the reduced expression of VDR is one of the drivers of BMSC senescence caused by an HFD.…”

Section: Discussionsupporting

confidence: 59%

Multiomics profiling reveals VDR as a central regulator of mesenchymal stem cell senescence with a known association with osteoporosis after high-fat diet exposure

Chen,

Kuang,

Cen

et al. 2024

Int J Oral Sci

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The consumption of a high-fat diet (HFD) has been linked to osteoporosis and an increased risk of fragility fractures. However, the specific mechanisms of HFD-induced osteoporosis are not fully understood. Our study shows that exposure to an HFD induces premature senescence in bone marrow mesenchymal stem cells (BMSCs), diminishing their proliferation and osteogenic capability, and thereby contributes to osteoporosis. Transcriptomic and chromatin accessibility analyses revealed the decreased chromatin accessibility of vitamin D receptor (VDR)-binding sequences and decreased VDR signaling in BMSCs from HFD-fed mice, suggesting that VDR is a key regulator of BMSC senescence. Notably, the administration of a VDR activator to HFD-fed mice rescued BMSC senescence and significantly improved osteogenesis, bone mass, and other bone parameters. Mechanistically, VDR activation reduced BMSC senescence by decreasing intracellular reactive oxygen species (ROS) levels and preserving mitochondrial function. Our findings not only elucidate the mechanisms by which an HFD induces BMSC senescence and associated osteoporosis but also offer new insights into treating HFD-induced osteoporosis by targeting the VDR-superoxide dismutase 2 (SOD2)-ROS axis.

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Section: Discussionsupporting

confidence: 59%

Multiomics profiling reveals VDR as a central regulator of mesenchymal stem cell senescence with a known association with osteoporosis after high-fat diet exposure

Chen,

Kuang,

Cen

et al. 2024

Int J Oral Sci

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“…Based on the canonical signaling of Wnt in activating neurogenesis in the brain and maintaining balance between activated neural stem cells (aNSC)/qNSC avoiding depletion, it is crucial to maintain persistent VDR activity. Therefore, deficiency in VitD could cause an imbalance in Wnt signaling and inhibit the gradual neural SC stimulation required to maintain a neurogenic rate [ 100 ]. However, more research is needed in this field to identify potential VDR agonists targeting neuronal SCs.…”

Section: Vitamin D and Its Potential Impact On The Biological Hallmar...mentioning

confidence: 99%

Targeting the Hallmarks of Aging with Vitamin D: Starting to Decode the Myth

Ruggiero,

Tafaro,

Cianferotti

et al. 2024

Nutrients

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Aging is the result of several complex and multifactorial processes, where several agents contribute to an increased intrinsic vulnerability and susceptibility to age-related diseases. The hallmarks of aging are a set of biological mechanisms that are finely regulated and strictly interconnected, initiating or contributing to biological changes and anticipating several age-related diseases. The complex network of cellular and intercellular connections between the hallmarks might represent a possible target for the research of agents with pleiotropic effects. Vitamin D (VitD) is known to have a positive impact not only on muscle and bone health but also on several extra-skeletal districts, due to the widespread presence of Vitamin D Receptors (VDRs). VitD and VDR could be molecules potentially targeting the hallmarks of the aging network. To date, evidence about the potential effects of VitD on the hallmarks of aging is scarce in humans and mainly based on preclinical models. Although underpowered and heterogeneous, in-human studies seem to confirm the modulatory effect of VitD on some hallmarks of aging and diseases. However, more investigations are needed to clarify the pleiotropic effects of VitD and its impact on the hallmark of aging, hopefully highlighting the courses for translational applications and potential clinical conclusions.

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“…Epidemiological observations have uncovered a neurosteroid hormone vitamin D deficiency in many patients with AD and impaired cognitive function [ 270 , 271 ]. The vitamin D receptor is present in the human brain in neuronal and glial cells, where its activation by vitamin D is important in brain development and function [ 272 , 273 , 274 ]. A prospective study of 1658 elderly persons without dementia followed for an average of 5.6 years found a substantial increase in the risk of developing AD and all-cause dementia with vitamin D deficiency [ 275 ].…”

Section: Diet As a Preventative Measurementioning

confidence: 99%

Alzheimer’s Disease Treatment: The Search for a Breakthrough

et al. 2023

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As the search for modalities to cure Alzheimer’s disease (AD) has made slow progress, research has now turned to innovative pathways involving neural and peripheral inflammation and neuro-regeneration. Widely used AD treatments provide only symptomatic relief without changing the disease course. The recently FDA-approved anti-amyloid drugs, aducanumab and lecanemab, have demonstrated unclear real-world efficacy with a substantial side effect profile. Interest is growing in targeting the early stages of AD before irreversible pathologic changes so that cognitive function and neuronal viability can be preserved. Neuroinflammation is a fundamental feature of AD that involves complex relationships among cerebral immune cells and pro-inflammatory cytokines, which could be altered pharmacologically by AD therapy. Here, we provide an overview of the manipulations attempted in pre-clinical experiments. These include inhibition of microglial receptors, attenuation of inflammation and enhancement of toxin-clearing autophagy. In addition, modulation of the microbiome-brain-gut axis, dietary changes, and increased mental and physical exercise are under evaluation as ways to optimize brain health. As the scientific and medical communities work together, new solutions may be on the horizon to slow or halt AD progression.

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Role of Neural Stem Cells and Vitamin D Receptor (VDR)–Mediated Cellular Signaling in the Mitigation of Neurological Diseases

Cited by 11 publications

References 320 publications

Multiomics profiling reveals VDR as a central regulator of mesenchymal stem cell senescence with a known association with osteoporosis after high-fat diet exposure

Multiomics profiling reveals VDR as a central regulator of mesenchymal stem cell senescence with a known association with osteoporosis after high-fat diet exposure

Targeting the Hallmarks of Aging with Vitamin D: Starting to Decode the Myth

Alzheimer’s Disease Treatment: The Search for a Breakthrough

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