An appraisal of folates as key factors in cognition and ageing-related diseases

Craenen, Kai; Verslegers, Mieke; Baatout, Sarah; Benotmane, Mohammed Abderrafi

doi:10.1080/10408398.2018.1549017

Cited by 15 publications

(14 citation statements)

References 183 publications

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“…These findings thus suggest that unmethylated HuD may lower the decay of this specific target transcript by forming a tighter complex with it. 47,48 With reference to AD, it would be interesting, for instance, to explore whether folic acid administration could be associated with HuD methylation and, in turn, with an accelerated decay of its specific target transcripts APP and BACE1.…”

Section: ■ Discussionmentioning

confidence: 99%

“…Of particular interest is the evidence that folic acid can act as a HuD-mRNA interfering compound, since it could clarify a still unknown mechanism of action of this widely used vitamin and could justify its use in the prevention of some neurodegenerative diseases. 48 Additional experiments are ongoing to deeply understand the biological outcomes resulting from HuD and folic acid interaction. In conclusion, our results pave the way toward the validation of HuD as a drug target and may open a novel route for the discovery of innovative agents to counteract neurodegenerative diseases.…”

Section: ■ Conclusionmentioning

confidence: 99%

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Identification of Compounds Targeting HuD. Another Brick in the Wall of Neurodegenerative Disease Treatment

et al. 2021

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ELAV-like (ELAVL) RNA-binding proteins play a pivotal role in post-transcriptional processes, and their dysregulation is involved in several pathologies. This work was focused on HuD (ELAVL4), which is specifically expressed in nervous tissues, and involved in differentiation and synaptic plasticity mechanisms. HuD represents a new, albeit unexplored, candidate target for the treatment of several relevant neurodegenerative diseases. The aim of this pioneering work was the identification of new molecules able to recognize and bind HuD, thus interfering with its activity. We combined virtual screening, molecular dynamics (MD), and STD-NMR techniques. Starting from around 51 000 compounds, four promising hits eventually provided experimental evidence of their ability to bind HuD. Among the selected best hits, folic acid was found to be the most interesting one, being able to well recognize the HuD binding site. Our results provide a basis for the identification of new HuD interfering compounds which may be useful against neurodegenerative syndromes.

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Section: ■ Discussionmentioning

confidence: 99%

Section: ■ Conclusionmentioning

confidence: 99%

Identification of Compounds Targeting HuD. Another Brick in the Wall of Neurodegenerative Disease Treatment

et al. 2021

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“…Folic acid and N5-methylTHF supplementation are beneficial in several medical conditions, most notably during early pregnancy to prevent neural tube defects. Optimal levels of folates are required for neuronal development, memory, and cognitive functions, and folates are also linked to aging-dependent neurodegenerative disorders [ 57 ]. For example, in the case of Alzheimer’s disease, the concentration of folate in the cerebrospinal fluid was found to be significantly reduced [ 58 ] and 1.25 mg/day folic acid treatment for 6 months was beneficial in a clinical trial [ 59 ].…”

Section: Hd Impacts Dna Methylation Writers Readers and Erasersmentioning

confidence: 99%

DNA Methylation in Huntington’s Disease

Zsindely

Siági

Bodai

2021

IJMS

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Methylation of cytosine in CpG dinucleotides is the major DNA modification in mammalian cells that is a key component of stable epigenetic marks. This modification, which on the one hand is reversible, while on the other hand, can be maintained through successive rounds of replication plays roles in gene regulation, genome maintenance, transgenerational epigenetic inheritance, and imprinting. Disturbed DNA methylation contributes to a wide array of human diseases from single-gene disorders to sporadic metabolic diseases or cancer. DNA methylation was also shown to affect several neurodegenerative disorders, including Huntington’s disease (HD), a fatal, monogenic inherited disease. HD is caused by a polyglutamine repeat expansion in the Huntingtin protein that brings about a multifaceted pathogenesis affecting several cellular processes. Research of the last decade found complex, genome-wide DNA methylation changes in HD pathogenesis that modulate transcriptional activity and genome stability. This article reviews current evidence that sheds light on the role of DNA methylation in HD.

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“…Folic acid (FA), a synthetic vitamin, is generally known to prevent NTDs [reviewed in Imbard et al (2013)], in addition to other defects such as heart defects and some skeletal defects (Kappen, 2013). Besides, FA has been suggested to prevent the development of age-related neurodegenerative diseases and overall cognition (Craenen et al, 2020a). Several countries enforce staple food fortification, whereas others support FA supplementation during pregnancy (Imbard et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Folic Acid Fortification Prevents Morphological and Behavioral Consequences of X-Ray Exposure During Neurulation

Craenen

Verslegers

Callaerts-Végh

et al. 2021

Front. Behav. Neurosci.

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Previous studies suggested a causal link between pre-natal exposure to ionizing radiation and birth defects such as microphthalmos and exencephaly. In mice, these defects arise primarily after high-dose X-irradiation during early neurulation. However, the impact of sublethal (low) X-ray doses during this early developmental time window on adult behavior and morphology of central nervous system structures is not known. In addition, the efficacy of folic acid (FA) in preventing radiation-induced birth defects and persistent radiation-induced anomalies has remained unexplored. To assess the efficacy of FA in preventing radiation-induced defects, pregnant C57BL6/J mice were X-irradiated at embryonic day (E)7.5 and were fed FA-fortified food. FA partially prevented radiation-induced (1.0 Gy) anophthalmos, exencephaly and gastroschisis at E18, and reduced the number of pre-natal deaths, fetal weight loss and defects in the cervical vertebrae resulting from irradiation. Furthermore, FA food fortification counteracted radiation-induced impairments in vision and olfaction, which were evidenced after exposure to doses ≥0.1 Gy. These findings coincided with the observation of a reduction in thickness of the retinal ganglion cell and nerve fiber layer, and a decreased axial length of the eye following exposure to 0.5 Gy. Finally, MRI studies revealed a volumetric decrease of the hippocampus, striatum, thalamus, midbrain and pons following 0.5 Gy irradiation, which could be partially ameliorated after FA food fortification. Altogether, our study is the first to offer detailed insights into the long-term consequences of X-ray exposure during neurulation, and supports the use of FA as a radioprotectant and antiteratogen to counter the detrimental effects of X-ray exposure during this crucial period of gestation.

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An appraisal of folates as key factors in cognition and ageing-related diseases

Cited by 15 publications

References 183 publications

Identification of Compounds Targeting HuD. Another Brick in the Wall of Neurodegenerative Disease Treatment

Identification of Compounds Targeting HuD. Another Brick in the Wall of Neurodegenerative Disease Treatment

DNA Methylation in Huntington’s Disease

Folic Acid Fortification Prevents Morphological and Behavioral Consequences of X-Ray Exposure During Neurulation

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