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Development of methods for testing drugs affecting the CNS
Hrabinová, Martina ; Jun, Daniel (advisor) ; Patočka, Jiří (referee)
1 Abstract and keywords The current thesis aims at the production of three enzymes, including beta-secretase 1 (BACE1; beta-site amyloid precursor protein cleaving enzyme 1), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). BACE1 is an integral membrane protein that plays a crucial role in the amyloid precursor protein's cleavage. The product is subsequently processed by y-secretase, producing amyloid-beta peptides and insoluble amyloid plaques in Alzheimer's patients (AD). According to the Annual Report of the Czech Alzheimer's Society, 158,000 patients were diagnosed in 2019. By 2050, this number is supposed to reach 300,000 patients. AChE inhibitors and N-methyl-D-aspartate receptor antagonists are currently the only alternatives for AD therapy. AChE is also a target enzyme in nerve agent (NA) poisoning (together with BChE). The Department of Toxicology and Military Pharmacy focuses on studying NA effects and medical protection against them. From this perspective, the production of AChE and BChE is essential for developing and evaluating newly synthesized cholinesterase (ChE) reactivators and inhibitors. The thesis focuses on introducing the expression system Expi293 to produce human recombinant enzymes BACE1, AChE, and BChE. For each enzyme, the individual steps required to obtain a...
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