Direct current stimulation enhances neuronal alpha-synuclein degradation in vitro

Abstract Despite transcranial Direct Current Stimulation (DCS) is currently proposed as a symptomatic treatment in Parkinson’s disease, the intracellular and molecular mechanisms elicited by this technique are still unknown, and its disease-modifying potential unexplored. Aim of this study was to el...

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Autores principales:	Gessica Sala, Tommaso Bocci, Valentina Borzì, Marta Parazzini, Alberto Priori, Carlo Ferrarese
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1c0943f210244504988764ecbc0f4a7b
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spelling	oai:doaj.org-article:1c0943f210244504988764ecbc0f4a7b2021-12-02T14:16:33ZDirect current stimulation enhances neuronal alpha-synuclein degradation in vitro10.1038/s41598-021-81693-82045-2322https://doaj.org/article/1c0943f210244504988764ecbc0f4a7b2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81693-8https://doaj.org/toc/2045-2322Abstract Despite transcranial Direct Current Stimulation (DCS) is currently proposed as a symptomatic treatment in Parkinson’s disease, the intracellular and molecular mechanisms elicited by this technique are still unknown, and its disease-modifying potential unexplored. Aim of this study was to elucidate the on-line and off-line effects of DCS on the expression, aggregation and degradation of alpha-synuclein (asyn) in a human neuroblastoma cell line under basal conditions and in presence of pharmachologically-induced increased asyn levels. Following DCS, gene and protein expression of asyn and its main autophagic catabolic pathways were assessed by real-time PCR and Western blot, extracellular asyn levels by Dot blot. We found that, under standard conditions, DCS increased monomeric and reduced oligomeric asyn forms, with a concomitant down-regulation of both macroautophagy and chaperone-mediated autophagy. Differently, in presence of rotenone-induced increased asyn, DCS efficiently counteracted asyn accumulation, not acting on its gene transcription, but potentiating its degradation. DCS also reduced intracellular and extracellular asyn levels, increased following lysosomal inhibition, independently from autophagic degradation, suggesting that other mechanisms are also involved. Collectively, these findings suggest that DCS exerts on-line and off-line effects on the expression, aggregation and autophagic degradation of asyn, indicating a till unknown neuroprotective role of tDCS.Gessica SalaTommaso BocciValentina BorzìMarta ParazziniAlberto PrioriCarlo FerrareseNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gessica Sala Tommaso Bocci Valentina Borzì Marta Parazzini Alberto Priori Carlo Ferrarese Direct current stimulation enhances neuronal alpha-synuclein degradation in vitro
description	Abstract Despite transcranial Direct Current Stimulation (DCS) is currently proposed as a symptomatic treatment in Parkinson’s disease, the intracellular and molecular mechanisms elicited by this technique are still unknown, and its disease-modifying potential unexplored. Aim of this study was to elucidate the on-line and off-line effects of DCS on the expression, aggregation and degradation of alpha-synuclein (asyn) in a human neuroblastoma cell line under basal conditions and in presence of pharmachologically-induced increased asyn levels. Following DCS, gene and protein expression of asyn and its main autophagic catabolic pathways were assessed by real-time PCR and Western blot, extracellular asyn levels by Dot blot. We found that, under standard conditions, DCS increased monomeric and reduced oligomeric asyn forms, with a concomitant down-regulation of both macroautophagy and chaperone-mediated autophagy. Differently, in presence of rotenone-induced increased asyn, DCS efficiently counteracted asyn accumulation, not acting on its gene transcription, but potentiating its degradation. DCS also reduced intracellular and extracellular asyn levels, increased following lysosomal inhibition, independently from autophagic degradation, suggesting that other mechanisms are also involved. Collectively, these findings suggest that DCS exerts on-line and off-line effects on the expression, aggregation and autophagic degradation of asyn, indicating a till unknown neuroprotective role of tDCS.
format	article
author	Gessica Sala Tommaso Bocci Valentina Borzì Marta Parazzini Alberto Priori Carlo Ferrarese
author_facet	Gessica Sala Tommaso Bocci Valentina Borzì Marta Parazzini Alberto Priori Carlo Ferrarese
author_sort	Gessica Sala
title	Direct current stimulation enhances neuronal alpha-synuclein degradation in vitro
title_short	Direct current stimulation enhances neuronal alpha-synuclein degradation in vitro
title_full	Direct current stimulation enhances neuronal alpha-synuclein degradation in vitro
title_fullStr	Direct current stimulation enhances neuronal alpha-synuclein degradation in vitro
title_full_unstemmed	Direct current stimulation enhances neuronal alpha-synuclein degradation in vitro
title_sort	direct current stimulation enhances neuronal alpha-synuclein degradation in vitro
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1c0943f210244504988764ecbc0f4a7b
work_keys_str_mv	AT gessicasala directcurrentstimulationenhancesneuronalalphasynucleindegradationinvitro AT tommasobocci directcurrentstimulationenhancesneuronalalphasynucleindegradationinvitro AT valentinaborzi directcurrentstimulationenhancesneuronalalphasynucleindegradationinvitro AT martaparazzini directcurrentstimulationenhancesneuronalalphasynucleindegradationinvitro AT albertopriori directcurrentstimulationenhancesneuronalalphasynucleindegradationinvitro AT carloferrarese directcurrentstimulationenhancesneuronalalphasynucleindegradationinvitro
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Direct current stimulation enhances neuronal alpha-synuclein degradation in vitro

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