The effect of monoamine oxidase A and B inhibitors on the phosphorylation of tau protein. Testing the potencial therapeutic effect in Alzheimers disease

Langer, Lea (2015) The effect of monoamine oxidase A and B inhibitors on the phosphorylation of tau protein. Testing the potencial therapeutic effect in Alzheimers disease. Diploma thesis, Faculty of Science > Department of Biology.

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Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by slowly progressing impairment of episodic memory. According to the tau hypothesis of AD, the dysfunction of tau protein leads to its separation from the microtubule, degeneration of axons and neuronal death. Tau protein is abnormally phosphorylated in AD at more than 40 sites, but the exact nature of causal sequence of events leading to this is not known. It is believed that an increased activity of activated monoamine oxidase (MAO) may have an important role in the early pathogenesis of AD. Due to the complexity of AD new drugs are developed that have the ability to simultaneously act on different targets, such as the new compound ASS234. It inhibits activity of MAO-A and MAO-B enzymes, and by acting on acetylcholinesterase (AChE) enzyme, it simultaneously reduces aggregation of β-amyloid protein. As ASS234 compound is synthesized from donepezil (AChE inhibitor) and PF901N (MAO-B inhibitor), it has demonstrated some expected positive effects for potential therapeutic use. The aim of this work was to find out how do MAO-B inhibitor PF9601N and inhibitor of MAO-A clorgyline affect the phosphorylation of tau protein. The results showed that clorgyline reduces phosphorylation of tau protein at Ser199 epitope in neuroblastoma cell culture SH-SY5Y, while such effect was not observed for PF9601N. These results could contribute to better understanding of the potential therapeutic effect of the inhibitors of MAO-A and MAO-B in AD, but for a more complete picture it is necessary to carry out further research on the impact of clorgyline on phosphorylation of the other epitopes of tau protein, especially Ser202/Thr205 and Ser396/Ser404.

Item Type: Thesis (Diploma thesis)
Keywords: Alzheimer's disease, hiperphosphorylation, PF9601N, klorgilin
Supervisor: Šimić, Goran
Co-supervisor: Hranilović, Dubravka
Date: 2015
Number of Pages: 52
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Grozdana Sirotic
Date Deposited: 17 Apr 2015 08:56
Last Modified: 17 Apr 2015 08:56
URI: http://digre.pmf.unizg.hr/id/eprint/3827

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