Accumulation of imidazolone, pentosidine and N^ɛ‐(carboxymethyl)lysine in hippocampal CA4 pyramidal neurons of aged human brain

Abstract

Previous studies from our laboratory demonstrated that N(epsilon)-(carboxymethyl)lysine (CML), one of the major advanced glycation end products (AGE), was accumulated in human pyramidal neurons in the hippocampus in an age-dependent manner. This suggests a potential link between AGE-accumulation and the aging process in neurons. The purpose of the present study was to examine whether this notion could be extended to other AGE structures, such as imidazolone and pentosidine. This was done using 19 human brains that were not affected by dementia. The immunohistochemical survey on distribution in brain tissues of imidazolone and pentosidine was carried out with monoclonal antibodies specific for imidazolone and pentosidine. A parallel control experiment was carried out with anti-CML antibody. The results showed that pentosidine and imidazolone were localized in neurons in different areas of human brain tissue, especially in neurons of CA4 in the hippocampus. The characteristic distribution of pentosidine and imidazolone is very similar to that of CML. Furthermore, when the accumulation of these AGE structures was compared with the age of individual brains it was found that accumulation of imidazolone, pentosidine and CML in the CA4 region increased with age. These findings taken together support the notion that the accumulation of AGE structures in the CA4 region might be closely related to the aging process in neurons.

Immunohistochemical localization of advanced glycation end products in pinguecula

“…AGEs is a generic name for the final reaction products of proteins and sugars [18]. Molecular analysis has revealed that AGEs-modified proteins have several specific molecular motifs, such asN " -(carboxymethyl)lysine (CML), pentosidine, imidazoline, and pyrraline [4,5,7]. These AGEsspecific motifs are speculated to have different roles in the ageing process and diabetic complications [18].…”

Flavan-3-ols Having a .GAMMA.-Lactam from the Roots of Actinidia arguta Inhibit the Formation of Advanced Glycation End Products in Vitro

“…6) Thus, the design and discovery of inhibitors of AGEs formation can offer a promising therapeutic approach for the prevention of diabetic or other pathogenic complications. Aminoguanidine, a hydrazine-like small molecule, is the first AGEs inhibitor explored in clinical trials.…”

Gamma-linolenic acid ameliorated glycation-induced memory impairment in rats

“…It states that the AGEs induced cross-linking of proteins which leads to age-associated decline in the cellular functions (Monnier 1988;Brownlee 1995). It has also been found that the level of AGEs increases with age, which co-relates with the development of various age-related pathologies like Alzheimer's disease (Jono et al 2002) and dementia (Yaffe et al 2011). Hence, the process of glycation provides therapeutic target to alleviate AGE-mediated harmful effects observed in senescence.…”

“…The non-enzymatic glycation theory states that the levels of advanced glycation end products (AGEs) increase with age, which leads to decline in cellular functions (Monnier 1988;Brownlee 1995;Jono et al 2002;Yaffe et al 2011). AGEs are the structurally modified proteins or lipids produced by non-enzymatic process termed as glycation.…”