ИСТИНА

Our work considers the interrelation between different types of protein glycation, glycolysis and the development of amyloid neurodegenerative diseases with aging [1; 2]. The primary focus is on the role of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase in changing the concentration of carbonyl compounds. An age-related increase in the glucose concentration and oxidative stress leading to "primary inactivation" of glyceraldehyde-3- phosphate dehydrogenase promote its glycation with aldehydes and a further irreversible decrease in its activity. Such a cycle can lead to numerous consequences - from the induction of apoptosis to glycation of amyloidogenic proteins [3]. Our efforts have been focused on the research of the effect of glycation on the pathological transformation of amyloidogenic proteins and peptides - beta-amyloid peptide, alpha-synuclein and prions. The modification of aggregates and fibrils is secondary in nature and does not play an important role in the development of neurodegenerative diseases. The glycation of amyloid proteins with carbonyl compounds can be one of the triggers of their transformation into toxic forms. We propose that the glycation of amyloidogenic proteins occurs with aging, which prevents proteins modification by ubiquitin and the SUMO proteins, disrupts degradation processes, and promotes the development of age-related neurodegenerative diseases. Prevention of glycation processes by lowering sugars concentrations in the organism, as well as by antioxidants may be an effective remedy for amyloid neurodegenerative diseases prophylaxis. В представленном сообщении мы приводим наши результаты о влиянии гликирования на альфа-синуклеин, выделенный в соответствии с опубликованным ранее методом(Barinova et al. Int J Biol Macromol. 2017) This work was supported by the RSF (No. 16-14-10027). 1) Muronetz VI , Barinova KV , Stroylova YY , Semenyuk PI , Schmalhausen EV (2017) Glyceraldehyde-3-phosphate dehydrogenase: Aggregation mechanisms and impact on amyloid neurodegenerative diseases. Int J Biol Macromol. 100:55-66. 2) Muronetz VI, Melnikova AK , Seferbekova ZN , Barinova KV , Schmalhausen EV . (2017) Glycation, Glycolysis, and Neurodegenerative Diseases: Is There Any Connection? Biochemistry (Mosc). 82(8):874-886. 3) Muronetz V, Barinova K, and Schmalhausen E (2017) Glycation of glyceraldehyde-3- phosphate dehydrogenase in the presence of glucose and glyceraldehyde-3-phosphate. Journal of the International Society of Antioxidants,3(2),1057. 4) Barinova KV, Kuravsky ML, Arutyunyan AM, Serebryakova MV, Schmalhausen EV, Muronetz VI. (2017) Dimerization of Tyr136Cys alpha-synuclein prevents amyloid transformation of wild type alpha-synuclein. Int J Biol Macromol, 96, p. 35-43.