Effects of neuronal calcium / calmodulin-dependent Protein Kinase 2 (CaMK-II) changes on the neurodegeneration process in the presence of β-amyloid peptide

Alzheimer's disease (AH), which is the most common form of dementia, is a progressive neurodegeneration condition in which cognitive dysfunction is observed. CaMK-II is a key enzyme in the creation of memory, and it is claimed to integrate temporary information specific to the dynamic nature of a "continuous" calcium signaling representing both past and present cellular activity. However, how the cellular activity / physiology was affected in the absence or exchange of the CaMK-II enzyme signal with its four isoforms has not yet been clearly defined. In this thesis, it was aimed to evaluate the effect of extracellular Aβ1-42 presence on neuronal CaMK-II isoform changes and cell viability by creating an in vitro Alzheimer model. The pre-aggregated Aβ1-42 peptide was applied to SH-SY5Y cells for 72 hours. In the presence and absence of CaMK-II enzyme inhibitor KN93, cell viability and calcium level in the cell culture medium were evaluated photometrically by MTT and LDH test. The m-RNA expression changes of CaMK-II enzyme alpha, beta, gamma and delta isoforms were determined using RT-PCR method. The changes of cellular beta and alpha isoforms were evaluated by ELISA method and immunofluorescence microscopy. Application of 10 µM Aβ1-42 decreased cell viability by 50% while increasing LDH release similarly (p <0.05). KN93 application did not have a protective effect against Aβ1-42 toxicity. Application of Aβ1-42 was found to significantly reduce CaMK-II enzyme mRNA expressions compared to the control group (p <0.05), causing alpha cellular accumulation of alpha isoform. According to our literature review, for the first time, it was shown that Aβ peptides can change the expression and level of isoforms of the enzyme CaMK-II at toxic concentrations. It can be thought that neuronal CaMK-II enzyme isoform changes are a critical step in cell survival and triggered to protect the cell itself.