Poster (download) Natalia Muraleva11Institute of Cytology and Genetics SB RAS Novosibirsk, Russia, myraleva@bionet.nsc.ru Accumulation of intracellular damage and protein aggregates is an universal hallmark of aging and accompanies the development of some age-related diseases include Alzheimer’s disease (AD). Alpha-B-Crystallin (CryaB) as the molecular chaperone contributes maintenance of proteostasis by prevention of aggregation of proteins (e.g. amyloid beta) and enables their correct refolding. CryaB activity is regulated by MAPK signaling pathway (MAPKsp) through its phosphorylation. Nevertheless, the link between changes in MAPK-dependent CryaB phosphorylation with age and the development of AD remains unclear. Here, we examined p38 MAPK- and ERK-dependent phosphorylation of CryaB in the brain of Wistar rats with normal aging and senescence-accelerated OXYS rats at the different stages of the development of AD-like pathology, including the presymptomatic stage.  The most significant changes identified in the p38 MAPK-dependent CryaB phosphorylation. The level of p-Ser59-CryaB in the brain of Wistar rats increased with the age on the background of p38-MAPKsp activation. Similar but more significant changes accompanied the development of AD-like pathology in OXYS rats. The activation of ERK1/2-dependent CryaB phosphorylation (p-Ser45-CryaB) was detected at the early age and at the late stages of AD-like pathology in OXYS, while changes in the ERK1/2 signaling pathway were detected in Wistar rats with age. Thus, alteration of MAPK-dependent phosphorylation CryaB occurs with the normal aging. Manifestation and progression of the signs of the AD occurs against the background of activation of p38MAPK-dependent phosphorylation of CryaB. Activation of EPK-dependent CryaB phosphorylation is characteristic of the preclinical and progressive stage of the AD-like pathology.

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