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1.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614176

RESUMO

The low effectiveness of symptomatic pharmacotherapy for Parkinson's disease (PD), which compensates for dopamine (DA) deficiency under degeneration of nigrostriatal dopaminergic (DAergic) neurons, could apparently be improved with neuroprotective therapy, which slows down neurodegeneration and PD progression. For this, it is necessary to have a DAergic cell line for the development of a PD model to screen neuroprotectors. We used immortalized human embryonic mesencephalon LUHMES cells (LCs) differentiated into DAergic neurons. The aim of this study was to characterize the phenotype of differentiated LCs and develop an 1-methyl-4-phenylpyridinium iodide (MPP+)-based test system for screening neuroprotectors. Using polymerase chain reaction (PCR) and immunocytochemistry, it has been shown that all differentiated LCs express genes and synthesize proteins characteristic of all neurons (microtubule-associated protein 2, bIII-tubulin, synaptotagmin 1) and specifically of DAergic neurons (tyrosine hydroxylase, aromatic L-amino acid decarboxylase, DA transporter, vesicular monoamine transporter 2). Furthermore, LCs are able to produce a small amount of DA, but under special conditions. To assess the mechanisms of neurodegeneration and neuroplasticity under the influence of toxins and antiparkinsonian drugs, including neuroprotectors, we have developed an LCs-based MPP+ PD model and proposed an original panel of markers for testing functional and structural cell disorders.


Assuntos
1-Metil-4-fenilpiridínio , Doença de Parkinson , Humanos , 1-Metil-4-fenilpiridínio/farmacologia , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Antiparkinsonianos/metabolismo , Fenótipo
2.
Molecules ; 26(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200418

RESUMO

This paper reports the synthesis of branched alkylene guanidines using microfluidic technologies. We describe the preparation of guanidine derivatives at lower temperatures, and with significantly less time than that required in the previously applicable method. Furthermore, the use of microfluidics allows the attainment of high-purity products with a low residual monomer content, which can expand the range of applications of this class of compounds. For all the samples obtained, the molecular-weight characteristics are calculated, based on which the optimal condensation conditions are established. Additionally, in this work, the antiviral activity of the alkylene guanidine salt against the SARS-CoV-2 virus is confirmed.


Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Guanidinas/síntese química , Guanidinas/farmacologia , Microfluídica/métodos , SARS-CoV-2/efeitos dos fármacos , Animais , COVID-19 , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Chlorocebus aethiops , Concentração Inibidora 50 , Espectrometria de Massas por Ionização por Electrospray , Células Vero
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