Review article
https://doi.org/10.21857/yq32ohxwv9
Interaction between oxidative stress and epigenetics decreases the low density lipoprotein receptor related protein 1 (LRP1) expression on the blood-brain barrier (BBB) in Alzheimer’s disease
Nikola Barić
Abstract
The aim of the study is to present and critically evaluate recent knowledge about the interaction be- tween oxidative stress and epigenetic mechanisms crucial for the developement and course of Alzhei- mer’s disease (AD), and it does not analyse the compound polygenetic AD etIology. While genetics investigates direct DNA (deoxyribonucleic acid) sequence alterations with hereditary changes of gene activities and functions, epigenetics is concerned with methylated changes without any changes in DNA sequences. Epigenetics does not deal with mutations, but exclusively with specific phenomena
as histone acetylation and deacetylation, histone methylation and demethylation, and especially DNA cytosine methylation and demethylation. All these epigenetic phenomena are tightly associated with specific enzymes. Histone acetylation is induced by enzyme histone acetyltransferase (HAT), and dea- cetylation by enzyme histone deacetylase (HDAC). Histone methylation is induced by enzyme histone methyltransferase (HMT), and demethylation by enzyme histone demethylase (HDM). Especially important epigenetic phenomena are DNA methylation and demethylation, where the first men- tioned phenomenon is induced by enzyme DNA cytosine methyltransferase (Dnmt), and the second by the combined effects of ten-eleven translocation (TET) family of dioxygenases and thymine DNA glycosylase (TDG). By the epigenetic DNA methylation mechanism, the Dnmt enzyme transports the methyl group (-CH3) from the S-adenyl methyonine (SAM) onto the C5 cytosyne position with the 5-methylcytosine formation. On the DNA molecule especially accentuated are the so called CpG islands, where their methylation leads to the disturbances of transcription factors binding, to the ac- cumulation of repressive methyl binding proteins and to the silencing gene expression. DNA dem- ethylation, as it is now viewed, is very complicated and is achieved by the interplay of DNA oxidative reactions and repair mechanisms. Recent studies emphasize the imortance of epigenetic mechanisms in the developement and course of AD. This study has the aim to primarily analyse the LRP1 gene methylation, as one of the crucial factors in AD pathophysiology. LRP1 receptor, dominantly located on the abluminal side of endothelial blood-brain barrier cells (BBB), is the major amyloid beta (Aβ) cleaner from the brain. According to a number of investigations, Aβ, accumulated and aggregated in the brain tissues, is the crucial factor in the onset and course of Alzheimer’s disease, the chronic, severe and lethal neurodegenerative disease.
Keywords
epigenetics; DNA methylation and demethylation; Alzheimer’s disease; LRP1 receptor; oxidative stress;
Hrčak ID:
290814
URI
Publication date:
18.12.2022.
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