Investigation of the Effects of Histone Acetyl-Transferase GCN5 Gene Knockout on Mitochondrial Homeostasis in Experimental Parkinson Model
Project no. 23271 · Status: Kapanmış · 2021
Summary
<p>Parkinson's Disease (PD) is a common neurodegenerative disease that occurs due to the loss of dopaminergic neurons in the <em>substantia nigra pars compacta</em> (SNpc) region of the brain. According to current statistical data, the etiology of this disease, which affects approximately 8.5 million people worldwide, is still not fully understood. On the other hand, findings obtained from studies conducted to elucidate the etiology of this disease indicate that disruptions in the functions of regulatory molecules such as PGC-1α, Parkin, Pink-1, MNF2 and Drp-1, which are associated with mitophagy and mitochondrial biogenesis processes that are responsible for maintaining mitochondrial homeostasis in cells, provides evidence that this condition may play a role in the neuropathogenesis of PD.</p><p>The main purpose of this thesis is to evaluate the effectiveness of GCN5 (General Control Non-repressed 5 protein) gene knockout, which has been shown to have inhibitory activity on PGC-1α, one of the main molecular actors in the regulation of mitochondrial biogenesis and mitophagy pathways, on <em>in vitro</em> and <em>in vivo</em> PD models induced by rotenone through the mitochondrial homeostasis process.</p><p>For this purpose, the effects of GCN5 gene knockout performed with gene-specific siRNA on primary dopaminergic neuron cells used as a PD model were evaluated by Real Time PCR analyses. The effects of GCN5 knockout on the <em>in vivo</em> PD model were evaluated with behavioral experiments, histochemical analyses, immunohistochemical analyses, Real Time PCR analyzes and biochemical analyses. Data from these analyzes show that GCN5 gene knockout with siRNA in PD models has a protective effect on dopaminergic neurons in the midbrain by regulating the expression levels of molecules involved in mitochondrial homeostasis and restoring antioxidant system activation.</p>