L-DOPA-quinone Mediated Recovery from GIRK Channel Firing Inhibition in Dopaminergic Neurons
| Autor: | Lorenzo Botta, Nicola Berretta, Raffaele Saladino, Daniela Aversa, Alessandro Barbieri, Nicola Biagio Mercuri, Giulio Poli, Bruno Mattia Bizzarri |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Protein subunit
Substantia nigra biological activity Protein degradation 01 natural sciences Biochemistry Settore CHIM/06 chemistry.chemical_compound dopaminergic neurons firing L-DOPA-quinone synthesis GIRK channel Drug Discovery medicine G protein-coupled inwardly-rectifying potassium channel Parkinson Alpha-synuclein 010405 organic chemistry Pars compacta Organic Chemistry Dopaminergic 0104 chemical sciences Cell biology nervous system diseases 010404 medicinal & biomolecular chemistry medicine.anatomical_structure chemistry nervous system Neuron |
| Popis: | [Image: see text] The oxidative degeneration of dopamine-releasing (DAergic) neurons in the substantia nigra pars compacta (SNc) has attracted much interest in preclinical research, due to its involvement in Parkinson’s disease manifestations. Evidence exists on the participation of quinone derivatives in mitochondrial dysfunction, alpha synuclein protein aggregation, and protein degradation. With the aim to investigate the role of L-DOPA-quinone in DAergic neuron functions, we synthesized L-DOPA-quinone by use of 2-iodoxybenzoic acid and measured its activity in recovery from dopamine-mediated firing inhibition of SNc neurons. Noteworthy, L-DOPA-quinone counteracts firing inhibition in SNc DAergic neurons caused by GIRK opening. A possible mechanism to explain the effect of L-DOPA-quinone on GIRK channel has been proposed by computational models. Overall, the study showed the possibility that L-DOPA-quinone stabilizes GIRK in a preopen conformation through formation of a covalent adduct with cysteine-65 on the GIRK2 subunit of the protein. |
| Databáze: | OpenAIRE |
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