AlphaB-crystallin modified by methylglyoxal prevents fibrillization of α-synuclein A53T

Barinova, K.V.; Medvedeva, M.V.; Serebryakova, M.V.; Kurochkina, L.P.; Muronetz, V.I.; Schmalhausen, E.V.

Авторы: Barinova K.V., Medvedeva M.V., Serebryakova M.V., Kurochkina L.P., Muronetz V.I., Schmalhausen E.V.
Журнал: Archives of Biochemistry and Biophysics
Том: 780
Год издания: 2026
Издательство: Academic Press
Местоположение издательства: United States
Первая страница: 1
Последняя страница: 12
Номер статьи: 110791
DOI: 10.1016/j.abb.2026.110791
Аннотация: AlphaB-crystallin is a small heat shock protein that is found in the eye lens, retina, heart, brain, skin, and skeletal muscle. Mutations of αB-crystallin lead to the development of cataracts, human muscle and heart disorders. The role of non-enzymatic glycation of αB-crystallin in the development of pathological processes has been little studied. The aim of this study was to evaluate the influence of enhanced methylglyoxal (MGO) level on the functions of αB-crystallin. We modified recombinant αB-crystallin (aB-Cr) by MGO and investigated the effect of this modification on different functions of aB-Cr: ability to suppress protein thermo-aggregation, promote proteinrefolding, and suppress the amyloid-like aggregation of α-synuclein A53T (αSynA53T, a mutation associated with early-onset Parkinson's disease). It was shown that MGO modifies 8 Arg residues per αB-Cr subunit yielding methylglyoxal-derived hydroimidazolone (MG-H) and results in cross-links between the protein subunits. Themodification reduces the ability of αB-Cr to suppress thermo-aggregation of catalase and to promote refolding glyceraldehyde-3-phosphate dehydrogenase. At the same time, modification by MGO enhances the ability of αBCr to suppress fibrillization of αSynA53T: while the addition of native αB-Cr results in shorter fibrils, MGOmodified αB-Cr completely prevents fibrillization of αSynA53T, yielding amorphous aggregates that are less toxic to the cells compared to αSynA53T fibrils. Therefore, the effect of MGO on various αB-crystallin functionsmay be different, resulting in a decrease or increase in its activity.
Добавил в систему: Муронец Владимир Израилевич

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