Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monoamine oxidase B (MAOB) is expressed in the mitochondrial membrane and has a key role in degrading various neurologically active amines such as benzylamine, phenethylamine and dopamine with the help of Flavin adenine dinucleotide (FAD) cofactor. The Parkinson's disease associated symptoms can be treated using inhibitors of MAO-B as the dopamine degradation can be reduced. Currently, many inhibitors are available having micromolar to nanomolar binding affinities. However, still there is demand for compounds with superior binding affinity and binding specificity with favorable pharmacokinetic properties for treating Parkinson's disease and computational screening methods can be majorly recruited for this. However, the accuracy of currently available force-field methods for ranking the inhibitors or lead drug-like compounds should be improved and novel methods for screening compounds need to be developed. We studied the performance of various force-field-based methods and data driven approaches in ranking about 3753 compounds having activity against the MAO-B target. The binding affinities computed using autodock and autodock-vina are shown to be non-reliable. The force-field-based MM-GBSA also under-performs. However, certain machine learning approaches, in particular KNN, are found to be superior, and we propose KNN as the most reliable approach for ranking the complexes to reasonable accuracy. Furthermore, all the employed machine learning approaches are also computationally less demanding.
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PMID:Performance of Force-Field- and Machine Learning-Based Scoring Functions in Ranking MAO-B Protein-Inhibitor Complexes in Relevance to Developing Parkinson's Therapeutics. 3308 Oct 86

In the experimental models of Parkinson's disease (PD), a well-known neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine or MPTP, pesticides like benomyl, paraquat,etc. are successfully used to induce a Parkinson's disease in human and nonhuman primates, which can be reversed by the drugs such as L-DOPA. A review on the alternative methods and alternative models in Parkinson's disease is documented here to understand their advantages and importance. Earlier researchers proved MPTP is effective in the goldfish, which reliably mirrors the neurochemical and behavioral changes caused by MPTP in the higher vertebrates. Gold fish brain has the "nucleus pars medialis," similar to the substanitia nigra of the human brain can be destructed by chemicals like MPTP, 6-hydroxydopamine and has selective protection by L-Dopa (Levodopa) and MAO-B (Monoamine oxidase B) inhibitors. In addition, zebrafish along with mice was successfully employed in the study of pesticides leading to neurodegeneration in PD. As the current animal models often couldn't replicate the true pathophysiology of idiopathic PD, alternative models have gained importance in the research. Upon having a glance at different models utilized in Parkinson's disease studies, one can get an idea on preferring alternative models, especially the zebra fish model in the study of neurodegenerative disorders.
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PMID:Teleost Model as an Alternative in Parkinson's Disease. 3310 37


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