Amiyotrofik lateral skleroz hastalığı için translasyon sonrası modifikasyonların biyobelirteç potansiyelinin ve terapötik hedeflerinin incelenmesi

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative and fatal disease that affects upper and lower motor neurons with damage to the motor neurons in the cortex, brainstem, and spinal cord regions. ALS results in death due to painless and progressive muscle weakness and respiratory failure after progression to paralysis from atrophy. Although there is an increased knowledge about ALS generated in a series of genetic and molecular pathological researches, the aetiology of many ALS cases is still unknown. The diagnosis of ALS is established through a comprehensive evaluation of the patient's medical history and clinical symptoms. These diagnostic methods can take a long time and be quite costly. Thus, the discovery of new biomarkers for the diagnosis of ALS is needed. Some recent studies have shown that post-translational modifications in several proteins may be indicative as biomarkers in the course of neurodegenerative diseases. This study aimed to investigate the post-translational modifications, such as ubiquitination and sumoylation II/III, of the proteins in the central nervous system (CNS) of B6SJL-Tg (SOD1G93A)1Gur /J) transgenic mouse model of ALS, as candidate biomarkers for the diagnosis of ALS. To compare the in vivo findings with the in vitro model, NSC-34 cells were mutated into SOD1G93A after neural differentiation. Proteome profiling via the 2D-PAGE method showed that there was a significant difference between proteins from 105-day-old transgenic mouse brains and wild-type mouse brains. As a result of LC-MS/MS analysis, this protein was determined to be a Rho-related GTP protein (Rhob). Post-translational modifications of proteins obtained from the in vivo and in vitro models were analyzed by the Simple Wes method and were found to have no ubiquitination and sumoylation II/III modifications within the range determined according to the target protein.