The effects of a novel monoamine oxidase B inhibitor in Parkinson's disease models

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide but even with its high prevalence, a complete cure to the disease still does not exist. One of the main causes of the disease is the selective loss of dopaminergic neurons in the substantia nigra pars compact (SNpc) which leads to a decrease in the level of dopamine in the brain. Monoamine oxidase (MAO) has received attention as a possible drug target in PD because of its function as an enzyme that metabolizes monoamines, especially dopamine. In this study, we used thirty-two newly developed MAO type B inhibitors (MAO-BI) to test their effects in in vitro and in vivo models of PD. As a screening process, lactate dehydrogenase (LDH) assay was performed to determine each MAO-BI’s cytotoxicity level and one MAO-BI showed protective property against the toxic environment induced by methyl-4-phenylpyridinium (MPP+). It was selected for administration in LRRK2G2019S transgenic mice and various behavior and biochemical tests were performed. We determined that the MAO-BI increased the latency to fall in LRRK2G2019S mice (MT mice) in the rotarod test and significantly increased the level of brain-derived neurotrophic factor (BDNF) in the striatum of littermate mice (LM mice). Also, the number of tyrosine hydroxylase (TH) positive neurons was increased in the substantia nigra pars compacta (SNpc) of MAO-BI administered MT mice compared to vehicle administered MT mice. Considering these results, we can conclude that the chemical structure utilized to synthesize the new MAO-BIs have potential as a therapeutic drug for PD treatment in the future.