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The Neurodegenerative Characteristics of Alzheimer’s Disease and Related Multi-Target Drug Design Studies
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Hayrettin Ozan Gülcan, Ilkay Erdogan Orhan
Monoamine oxidase (MAO) enzyme activity is one of the critical steps in the control of the function of several neurotransmitters (e.g., serotonin, dopamine, and norepinephrine). In other words, through the formation of aldehyde derivatives of neurotransmitters via MAO catalyzed oxidative deamination reactions, the amine neurotransmitters are deactivated (Shih et al., 1999). There are two types of MAO enzymes in human, as referred to as MAO-A and MAO-B. They display different tissue distribution and ratios depending on age. Although they are capable of employing a diverse amine substrates, there is some selectivity difference. MAO-A shows selectivity for serotonin, melatonin, norepinephrine, and epinephrine, while MAO-B possesses substrate selectivity for benzylamine and phenethylamine. On the other hand, both enzymes display similar characteristics to catalyze dopamine, tyramine, and tryptamine oxidative deamination reactions (Kalgutkar et al., 2001). Depending on the substrate specificity difference, MAO-A inhibition is mainly preferred as an option in the treatment of some form depression (e.g., to increase the available levels of serotonin, norepinephrine, and dopamine) (Meyer et al., 2006). Parkinson disease–related symptoms are generally related to deficiency of dopamine. Regarding the side effects of MAO-A inhibitors, MAO-B inhibitors (e.g., rasagiline, selegiline) are preferred to increase the available amount of dopamine in CNS (Youdim, 2006).
Drugs for Treatment of Neurological and Psychological Conditions
Published in Richard J. Sundberg, The Chemical Century, 2017
The crucial role of adrenaline, nor-adrenaline, dopamine, serotonin, and GABA as neurotransmitters made them appealing targets in the search for other drugs for treatment of neurological and psychological disorders. The general hypothesis that developed was that the levels of the neurotransmitters affected mood and behavior. In particular, deficiencies in the monoamine neurotransmitters were associated with depression. The observation that an antituberculosis drug, iproniazid had antidepressant effects, based on inhibition of the enzyme monoamine oxidase (MAO), led to one group of antidepressants called monoamine oxidase inhibitors (MAOI). Other drugs that had no MAOI activity were found to have antidepressant activity, such as imipramine. Its activity was found to be associated with the inhibition of uptake of noradrenaline at synapses. This led to discovery of other drugs that were both non-selective and selective among the neurotransmitters. They are classified as monoamine uptake inhibitors.
Xenobiotic metabolism and transport in Caenorhabditis elegans
Published in Journal of Toxicology and Environmental Health, Part B, 2021
Jessica H. Hartman, Samuel J. Widmayer, Christina M. Bergemann, Dillon E. King, Katherine S. Morton, Riccardo F. Romersi, Laura E. Jameson, Maxwell C. K. Leung, Erik C. Andersen, Stefan Taubert, Joel N. Meyer
Monoamine neurotransmitters such as dopamine and serotonin are degraded in humans by monoamine oxidases MAO-A and MAO-B. These enzymes also act on xenobiotics that are structurally similar to their natural substrates. C. elegans has a single ortholog of these genes, amx-2 (Schmid et al. 2015), which was demonstrated to metabolize serotonin in the worm (Wang et al. 2017) and presumably would have overlapping specificity with MAO-metabolized xenobiotics identified in mammalian systems.
Development and butyrylcholinesterase/monoamine oxidase inhibition potential of PVA-Moringa oleifera developed nanofibers
Published in Journal of Experimental Nanoscience, 2022
Nihal Abdalla Ibrahim, Saima Bibi, Abida Kalsoom Khan, Ghulam Murtaza
Enzymes are biologically active substances or proteins that catalyze various metabolic reactions in the human body. They possess active sites on which substrate can attach. Many metabolic imbalances are observed due to the activity of enzymes, so enzymes inhibition is required. Inhibitors are chemical compounds that can bind on active sites and stop the binding of the substrate with enzyme/s active site and cause hindrance for enzymes to catalyze the chemical reaction. High or low levels of butyrylcholinesterase (BuChE), monoamine oxidase A (MAO A) and monoamine oxidase B (MAO B) enzymes have been involved in many neuropsychiatric disorders, such as Parkinson’s disease, Alzheimer’s disease and depression [2]. These enzymes are important binding proteases or flavin (FAD) present in the outer mitochondrial membrane. MAO are responsible for the oxidation of monoamines such as dopamine, adrenaline, norepinephrine, serotonin. BuChE cause loss of cholinergic neurons by degradation of acetylcholine into acetate and thiocholine [3]. This degradation of neurotransmitters leads to neurological disorders like depression and Alzheimer. Therefore, there is a need to inhibit these enzymes by using alternative inhibitors to reduce neuropsychiatric disorders. Medicinal plants are an important source for the treatment of neurological disorders. Bioactive components like flavonoids and alkaloids present in plants have good potential to inhibit these enzymes. Alam et al. investigated the natural enzymes inhibators with antidiabetic property. They studied the enzymes responsible for diabetic disease and find the natural source to inhibit these enzymes as antidiabetic drug [5]. Fais et al. examined the enzyme inhibitory potential of Euphorbia characias extract towards α-amylase and α-glucosidase responsible for metabolic disorders [6]. A lot of work has been performed on the enzyme inhibitory effect of various plant extracts for pharmaceutical applications. However, no study has yet described the enzyme inhibition behavior of M. oleifera nanofibers.