Elektrik stimülasyonunun caenorhabditis elegans proteotoksik modeller üzerindeki etkilerinin incelenmesi

Huntington's disease (HD) is one of the nine fatal neurodegenerative diseases in which increase in CAG repeats (CAGn) in coding region leads to polyglutamine (polyQ) expansion in protein sequence. PolyQ expansion is the key factor for misfolded protein formation in neurons, causing the disease progression. For example, individuals with less than 35 CAG repeats do not possess any of the symptoms whereas the ones with more than 40 repeats show variety of them. Up to date, no specific and well-defined treatment for HD has been developed. Patients in latter stages need assistance in their daily activities which put great economic burden of the societies. Therefore, more effective therapeutic interventions to attenuate the symptoms of HD are needed. One approach to HD therapy is targeting misfolded protein through activation of the Heat-Shock Proteins (HSPs). They are conserved proteins, expressed in the presence of distinct stress conditions. They aid in protein assembly, proper folding and translocation. HSPs are divided into 5 groups based on their molecular weight: HSP100, HSP90, HSP70, HSP60, and the small HSPs. It is known that under stress conditions HSP expression is induced by transcription factors (Tf) like Heat Shock Transcription Factor-1 (HSF-1). Some of the current studies focus on augmenting HSP level to intervene aggregation-related diseases. Recently it has been shown that mild electrical stimulation (MES) has positive impact on wound healing, psychological diseases, neuromuscular activity, decrease in inflammation and decrease of pain. Most importantly, ES also influences the expression of HSPs. For example, ES significantly increase the expression level of HSP70 and HSP72 in mouse myoblasts (C2C12) and adenocarcinoma (A549) cell lines, respectively. Similar observation has been made with ES treated rat brain, which shows an increase in the mRNA levels of HSP70 and HSP90.C. elegans is a 1mm-long soil-nematode which is widely-used model organism, since their first introduction to research by Sydney Brenner in 1963. C. elegans has several advantages. For example, 83 percent of its genome including HSP genes is conserved among species. Additionally, transgenic insertion of corresponding disease gene like polyQs enables visualization of processes like aggregation, degeneration in this multicellular organism. The purpose of the current study was to test whether ES can be used as a therapeutic intervention in proteotoxic models. For this purpose, we first examined the influence of ES on C. elegans. We investigated the ability of ES treatment to increase the HSP expression in nematodes and to alleviate the disease severity in various frequencies. Key words: Mild electrical stimulation, C. elegans, Huntington's Disease, polyglutamine, lifespan, heat shock proteins.