Proliferation versus Differentiation: Redefining Retinoic Acid’s Role

Mosher, Kira Irving; Schaffer, David V.

doi:10.1016/j.stemcr.2018.05.011

Cited by 13 publications

(5 citation statements)

References 9 publications

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“…Due to the limited knowledge in the area of carotenoid metabolites, functioning as ligands of nuclear hormone ligands and further signalling, it should be discussed whether more ligands and more nuclear hormone mediated signalling is purely seen as beneficial or might also be seen as detrimental for human health. RAR-mediated signalling is responsible for a large variety of physiologically mediated pathways, ranging from central physiological pathways such as the induction of differentiation (352,353) , apoptosis (354,355) , cell cycle control (356)(357)(358) , lipid homeostasis (187,359,360) and proliferation (352,361) , which are of high importance for processes of embryonic development (362,363) , reproduction (364,365) , epidermal homeostasis and regeneration (366,367) , immune responses (368,369) and maintenance of bone, brain, nervous and cardiovascular functions (370)(371)(372) . Too low or too high levels of endogenous ATRA (373) , due to a dysfunctional or stressed retinoid homeostasis, while hard to define what the upper and lower threshold levels are, were seen to be risk factors for various previously mentioned physiological functions and are associated with further disease development, where retinoid signalling is dysfunctional.…”

Section: Carotenoids and Cancermentioning

confidence: 99%

Mechanistic aspects of carotenoid health benefits – where are we now?

et al. 2021

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Dietary intake and tissue levels of carotenoids have been associated with a reduced risk of several chronic diseases, including cardiovascular diseases, type 2 diabetes, obesity, brain related diseases and some types of cancer. However, intervention trials with isolated carotenoid supplements have mostly failed to confirm the postulated health benefits. It has thereby been speculated that dosing, matrix and synergistic effects, as well as underlying health and the individual nutritional status plus genetic background do play a role. It appears that our knowledge on carotenoid-mediated health benefits may still be incomplete, as the underlying mechanisms of action are poorly understood in relation to human relevance. Antioxidant mechanisms – direct or via transcription factors such as NRF2 and NF-κB - and activation of nuclear hormone receptor pathways such as of RAR/RXR or also PPARs, via carotenoid-metabolites, are the basic principles which we try to connect with carotenoid-transmitted health benefits as exemplified with described common diseases including obesity/diabetes and cancer. Depending on the targeted diseases, single or multiple mechanisms of actions may play a role. In this review and position paper, we try to highlight our present knowledge on carotenoid metabolism and mechanisms translatable into health benefits related to several chronic diseases.

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Section: Carotenoids and Cancermentioning

confidence: 99%

Mechanistic aspects of carotenoid health benefits – where are we now?

et al. 2021

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“…Transcription is regulated by the binding of RA to its receptor, RA receptor ( RAR ), which forms a complex with the retinoid X receptor ( RXR ) [ 36 ]. The RA is involved in the differentiation of NSCs into neurons, astrocytes, or oligodendrocytes [ 37 ]. RA activates the Hox gene, which is required for hindbrain development and regulates the head–trunk transition [ 38 ].…”

Section: Inhibiting the Smad Pathway In Ipscs For Neural Differentiationmentioning

confidence: 99%

Neuronal Cell Differentiation of iPSCs for the Clinical Treatment of Neurological Diseases

Lee,

Lee

et al. 2024

Biomedicines

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Current chemical treatments for cerebrovascular disease and neurological disorders have limited efficacy in tissue repair and functional restoration. Induced pluripotent stem cells (iPSCs) present a promising avenue in regenerative medicine for addressing neurological conditions. iPSCs, which are capable of reprogramming adult cells to regain pluripotency, offer the potential for patient-specific, personalized therapies. The modulation of molecular mechanisms through specific growth factor inhibition and signaling pathways can direct iPSCs’ differentiation into neural stem cells (NSCs). These include employing bone morphogenetic protein-4 (BMP-4), transforming growth factor-beta (TGFβ), and Sma-and Mad-related protein (SMAD) signaling. iPSC-derived NSCs can subsequently differentiate into various neuron types, each performing distinct functions. Cell transplantation underscores the potential of iPSC-derived NSCs to treat neurodegenerative diseases such as Parkinson’s disease and points to future research directions for optimizing differentiation protocols and enhancing clinical applications.

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“…Recent studies have shown that RA induces proliferation in early neurogenesis in the developing mouse cerebral cortex and adult hippocampus ( Mosher and Schaffer, 2018 ). Additionally, it was found that in stem-like glioma cells, RA promotes proliferation ( Choschzick et al, 2014 ; Haushalter et al, 2017 ; Mishra et al, 2018 ).…”

Section: Retinoic Acid and Its Signaling Mechanismmentioning

confidence: 99%

Targeting the retinoic acid signaling pathway as a modern precision therapy against cancers

Lavudi,

Nuguri,

Olverson

et al. 2023

Front. Cell Dev. Biol.

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Retinoic acid (RA) is a vital metabolite derived from vitamin A. RA plays a prominent role during development, which helps in embryological advancement and cellular differentiation. Mechanistically, RA binds to its definite nuclear receptors including the retinoic acid receptor and retinoid X receptor, thus triggering gene transcription and further consequences in gene regulation. This functional heterodimer activation later results in gene activation/inactivation. Several reports have been published related to the detailed embryonic and developmental role of retinoic acids and as an anti-cancer drug for specific cancers, including acute promyelocytic leukemia, breast cancer, and prostate cancer. Nonetheless, the other side of all-trans retinoic acid (ATRA) has not been explored widely yet. In this review, we focused on the role of the RA pathway and its downstream gene activation in relation to cancer progression. Furthermore, we explored the ways of targeting the retinoic acid pathway by focusing on the dual role of aldehyde dehydrogenase (ALDH) family enzymes. Combination strategies by combining RA targets with ALDH-specific targets make the tumor cells sensitive to the treatment and improve the progression-free survival of the patients. In addition to the genomic effects of ATRA, we also highlighted the role of ATRA in non-canonical mechanisms as an immune checkpoint inhibitor, thus targeting the immune oncological perspective of cancer treatments in the current era. The role of ATRA in activating independent mechanisms is also explained in this review. This review also highlights the current clinical trials of ATRA in combination with other chemotherapeutic drugs and explains the future directional insights related to ATRA usage.

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Proliferation versus Differentiation: Redefining Retinoic Acid’s Role

Cited by 13 publications

References 9 publications

Mechanistic aspects of carotenoid health benefits – where are we now?

Mechanistic aspects of carotenoid health benefits – where are we now?

Neuronal Cell Differentiation of iPSCs for the Clinical Treatment of Neurological Diseases

Targeting the retinoic acid signaling pathway as a modern precision therapy against cancers

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