Pregledni rad
Possible role of the low density lipoprotein receptor related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) in the ageing process of the human organism
Nikola Barić
; Private Family Medicine Practice in Labin, Presika 153, 52220 Labin, Croatia
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* Dopisni autor.
Sažetak
The analysis of the role of epigenetics in the pathophysiology of Alzheimer's disease (AD) emphasizes the crucial importance of the two large transmembrane receptors, the low- density lipoprotein receptor - related protein 1 (LRP1) and the receptor for advanced glycation end products (RAGE). In addition to the strong effects these two receptors have on the amyloid beta (Aβ) metabolism, it seems that they also cause the crucial events related to the process of the programmed ageing of the human organism. The ageing process can be broken down into two closely interwoven components: biological, i.e. normal or physiological ageing, driven by a defined epigenetic/genetic programme, and pathological or accelerated ageing, defined by the influence of primarily chronic uncontagious diseases. Presently, a number of theories are trying to answer the crucial questions, how and why this inevitable and complex biological process takes place in all living beings. On one side there are different variations of the programmed ageing theory, and on the other side there are ageing theories based on chronic damages of organism structures and functions that through time lead to irreparable damages, decline of adaptive capacities, weakening of a number of vital functions and in the end inevitable death. Without entering in the counting and description of the all til today known theories, the most recent experimental researches emphasize epigenetics as the crucial factor in this compound, unstoppable and essentially purposeful process.The close connection between the process of ageing and Alzheimer's disease (AD), and the role of low-density lipoprotein receptor-related protein1 (LRP1) receptor, and the receptor for advanced glycation end products (RAGE) in this degenerative disease imply the question of the possible role of these two outstanding transmembraneous multifunctional receptors with numerous ligands in the ageing process. LRP1 receptor is particularly sensitive to epigenetic factors. Due to abundant methylation, its gene (location 12q13.3), is suppressed with the transcription drop, accompanied by the disorder of its many functions, especially those linked to the drainage of harmful, toxic macromolecules from the brain. The continuing strong DNA methylation of the LRP1 gene promoter (insertion of the -CH3 methyl group onto C5 cytosine template strand of DNA) progressing during the life cycle, could be the crucial factor in the weakening of numerous processes, all of which have an impact in the accelerated ageing course of living beings. The exceptionally weak methylation of RAGE promoter (gene location 6p21.32), also has a strong impact on the ageing acceleration. This study primarily deals with the essence of the normal biological, i.e. physiological ageing, and tries to avoid as much as possible the impact of the other component- pathological ageing.
Ključne riječi
biological and pathological ageing; ageing theories; Alzheimer's disease; LRP1 receptor; RAGE receptor; epigenetics; DNA methyltransferase; methylation
Hrčak ID:
318620
URI
Datum izdavanja:
25.6.2024.
Posjeta: 148 *