Investigation of neuroprotective effects of probiotic derived exopolysaccharides in Alzheimer's disease model generated in SH-SY5Y neuroblastoma cells with amyloid beta 1-42

The purpose of this doctorate thesis is to investigate the neuroprotective effects of probiotic-derived (Lactobacillus delbrueckii ssp. bulgaricus B3 and Lactiplantibacillus plantarum GD2) lyopilized exopolysaccharides (L-EPSs) in an Alzheimer's disease (AD) model formed by amyloid beta (Aβ)1-42 in SH-SY5Y neuroblastoma cells. L-EPS quantities were determined, and their characterization was performed. The antioxidant activities of L-EPSs and their inhibitor effects on Aβ1-42 aggregation were determined. In an AD model formed with Aβ1-42, the neural protective effects of EPSs against cell death, effects on acetylcholine esterase (AChE) and antioxidant enzyme activities, and effects on total antioxidant status (TAS) and total oxidant status (TOS) were determined. In addition to the repressive effects of L-EPSs on the intracellular quantity of reactive oxygen species (ROS), their anti-apoptotic effects and effects on mitochondrial membrane potential (MMP) were also determined. The effects of L-EPSs on 14 different genes were determined. It was found that the L-EPSs used in the study were produced in high quantities. The elementary percentages and the fourier transform infrared spectroscopy (FTIR) spectra of the EPSs were determined. According to the atomic force microscope (AFM) and scanning electron microscope (SEM) images, the surface morphologies of the L-EPSs showed differences as granular and porous. According to their X-ray diffractometer (XRD) patterns, the L-EPSs were found to have amorphous character. L-EPSs were shown to exert antioxidant activity (p<0.05). L-EPSs were found to enhance cellular viability, TAS, antioxidant enzyme activities, MMP percentage, expression levels of the BCL2 and protein kinase B (AKT/PKB) genes (p<0.05). L-EPSs were found to reduce AChE, Aβ1-42 aggregation, TOS, intracellular ROS quantity, apoptotic cell percentage, expression levels of the BCL2 associated X (BAX), caspase-3 (CASP3), caspase-7 (CASP7), caspase-8 (CASP8), caspase-9 (CASP9), cytochrome C (CYCS), extracellular signal-regulated kinase 1 (ERK1), extracellular signal-regulated kinase 2 (ERK2), c-Jun N-Terminal kinase (JNK), JUN, nuclear factor-κB (NF-κB/p65), and p38 mitogen-activated protein kinase (p38 MAPK) genes (p<0.05). A review of all findings obtained in the study revealed that the L-EPS derived from the B3 strain came to the fore. In addition, it has been observed that the characteristic structure and surface morphology of L-EPSs are effective in neural protection. L-EPSs, whose mechanism of action has been demonstrated and has a high effect compared to its alternatives, has the potential to be a new drug active ingredient in the prevention and treatment of AD.