The investigation of mitochondria-specific antioxidant MitoQ on mitochondrial dysfunction at Alzheimer's disease cell line model

There is an increase in the incidence of neurodegenerative diseases in the community with the prolongation of the average life span This situation both negatively affects the life quality of the individuals and is a great burden for the healthcare sector. Alzheimer's disease (AD), a common form of Dementia, is a progressive disease associated with premature death of neurons. Today, approximately 36 million people are affected by AD and it is estimated to affect 115 million people in 2050. AD is a disease that can be triggered by genetic and environmental factors. The life quality of patients with AD falls drastically with the progression of the disease, and the patients become in need of care. These patients are also lost in the advanced stage with considerable impairment of brain functions. For AD treatment, 244 drugs have been developed since 1998; however, only donepezil, rivastigmine, galantamine and memantine are used. There are 5 hypotheses that are believed to be valid for the emergence of AD. These; hereditary transmission, decrease in the synthesis of acetylcholine, neurotoxic effects of Aβ (amyloid-beta) accumulation in the brain, neurofibrillary tangle formation in the brain due to hyperphosphorylated tau, impaired mitochondrial dynamics and functions. Aβ plaques blocks communication between neurons and tau tangles prevents food and essential molecules intake. It is emphasized that mitochondrial dysfunction observed in early stages of AD may be the cause of the disease. And, it is thought that it may enable the early diagnosis and treatment of the disease. Mitochondria is a organelle carrying its own genetic material. Mitochondrial DNA (mtDNA) encodes 13 of 80 proteins required for electron transport in the respiratory chain. It has been shown that some mitochondrial functions are affected in AD. Some of these functions are reduction in glucose metabolism, mitochondrial enzymatic damage, increase in the production of ROS before formation of Aβ plaques and tau neurofibrillary tangles. The changes detected in mitochondria dynamics are deterioration of mitochondrial fission and fusion balance, decrease in transport of mitochondria on axons, decline in intracellular mitochondria and deformations. In this thesis, the relationship between mitochondrial dysfunction and the pathogenesis of AD is planned to be clarified to contribute to the identification of the mechanism of AD and develop potential therapeutic targets. For this purpose, Aβ42-induced in vitro AD model was developed and MitoQ, a mitochondrial targeted antioxidant agent, was treated to these cells. Alzheimer, mitochondria and oxidative stress related genes were investigated. The analysis revealed that the negative effects of Aβ42 on neuroblastoma cells and mitochondrial dysfunction were ameliorated by the antioxidant characteristic of MitoQ molecule.