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Development of novel cholinesterase modulators
Górecki, Lukáš ; Korábečný, Jan (advisor) ; Mičuda, Stanislav (referee) ; Roh, Jaroslav (referee)
Tittle: Development of novel cholinesterase modulators Author: Mgr. Lukáš Górecki Abstract The enzyme acetylcholinesterase (AChE) is a key component in cholinergic synapses and at the neuromuscular junctions. Its physiological function is essential in humans, as well as in animal species, including insects. In pathological conditions, AChE is also involved in various disorders such as Alzheimer's disease (AD) or myasthenia gravis. The significance of the enzyme has also been demonstrated by its successful use as a target in insecticides. In addition, it is the key mediator in the manifestation of symptoms of intoxication after exposure to Chemical warfare agents (CWA) (Nerve agents; NA). Herein, I report my study of three different aspects of this enzyme: as an anti-AD target; as an insecticidal target; and as an enzyme to be reactivated after intoxication by organophosphorus compounds (OPCs). Since the introduction of tacrine in 1993 as an anti-AD drug, much attention has been paid to the development of novel AChE inhibitors; some, such as donepezil, have been successfully marketed. At present, there is still a need for efficient drugs against AD. As AD is a multifactorial disorder, it believed that it cannot be treated by simply targeting one pathological condition. Therefore, the so-called multi-target...
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