Anti-Aggregative Effect of the Antioxidant DJ-1 on the TPPP/p25-Derived Pathological Associations of Alpha-Synuclein

DJ-1, a multi-functional protein with antioxidant properties, protects dopaminergic neurons against Parkinson’s disease (PD). The oligomerization/assembly of alpha-synuclein (SYN), promoted by Tubulin Polymerization Promoting Protein (TPPP/p25), is fatal in the early stage of PD. The pathological as...

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Autores principales:	Judit Oláh, Attila Lehotzky, Tibor Szénási, Judit Ovádi
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	alpha-synuclein TPPP/p25 DJ-1 parkinsonism anti-aggregative effect BiFC Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4895946aa1604e69b8204e8ea43c0786
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spelling	oai:doaj.org-article:4895946aa1604e69b8204e8ea43c07862021-11-25T17:08:48ZAnti-Aggregative Effect of the Antioxidant DJ-1 on the TPPP/p25-Derived Pathological Associations of Alpha-Synuclein10.3390/cells101129092073-4409https://doaj.org/article/4895946aa1604e69b8204e8ea43c07862021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2909https://doaj.org/toc/2073-4409DJ-1, a multi-functional protein with antioxidant properties, protects dopaminergic neurons against Parkinson’s disease (PD). The oligomerization/assembly of alpha-synuclein (SYN), promoted by Tubulin Polymerization Promoting Protein (TPPP/p25), is fatal in the early stage of PD. The pathological assembly of SYN with TPPP/p25 inhibits their proteolytic degradation. In this work, we identified DJ-1 as a new interactive partner of TPPP/p25, and revealed its influence on the association of TPPP/p25 with SYN. DJ-1 did not affect the TPPP/p25-derived tubulin polymerization; however, it did impede the toxic assembly of TPPP/p25 with SYN. The interaction of DJ-1 with TPPP/p25 was visualized in living human cells by fluorescence confocal microscopy coupled with Bifunctional Fluorescence Complementation (BiFC). While the transfected DJ-1 displayed homogeneous intracellular distribution, the TPPP/p25-DJ-1 complex was aligned along the microtubule network. The anti-aggregative effect of DJ-1 on the pathological TPPP/p25-SYN assemblies was established by the decrease in the intensity of their intracellular fluorescence (BiFC signal) and the increase in the proteolytic degradation of SYN complexed with TPPP/p25 due to the DJ-1-derived disassembly of SYN with TPPP/p25. These data obtained with HeLa and SH-SY5Y cells revealed the protective effect of DJ-1 against toxic SYN assemblies, which assigns a new function to the antioxidant sensor DJ-1.Judit OláhAttila LehotzkyTibor SzénásiJudit OvádiMDPI AGarticlealpha-synucleinTPPP/p25DJ-1parkinsonismanti-aggregative effectBiFCBiology (General)QH301-705.5ENCells, Vol 10, Iss 2909, p 2909 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	alpha-synuclein TPPP/p25 DJ-1 parkinsonism anti-aggregative effect BiFC Biology (General) QH301-705.5
spellingShingle	alpha-synuclein TPPP/p25 DJ-1 parkinsonism anti-aggregative effect BiFC Biology (General) QH301-705.5 Judit Oláh Attila Lehotzky Tibor Szénási Judit Ovádi Anti-Aggregative Effect of the Antioxidant DJ-1 on the TPPP/p25-Derived Pathological Associations of Alpha-Synuclein
description	DJ-1, a multi-functional protein with antioxidant properties, protects dopaminergic neurons against Parkinson’s disease (PD). The oligomerization/assembly of alpha-synuclein (SYN), promoted by Tubulin Polymerization Promoting Protein (TPPP/p25), is fatal in the early stage of PD. The pathological assembly of SYN with TPPP/p25 inhibits their proteolytic degradation. In this work, we identified DJ-1 as a new interactive partner of TPPP/p25, and revealed its influence on the association of TPPP/p25 with SYN. DJ-1 did not affect the TPPP/p25-derived tubulin polymerization; however, it did impede the toxic assembly of TPPP/p25 with SYN. The interaction of DJ-1 with TPPP/p25 was visualized in living human cells by fluorescence confocal microscopy coupled with Bifunctional Fluorescence Complementation (BiFC). While the transfected DJ-1 displayed homogeneous intracellular distribution, the TPPP/p25-DJ-1 complex was aligned along the microtubule network. The anti-aggregative effect of DJ-1 on the pathological TPPP/p25-SYN assemblies was established by the decrease in the intensity of their intracellular fluorescence (BiFC signal) and the increase in the proteolytic degradation of SYN complexed with TPPP/p25 due to the DJ-1-derived disassembly of SYN with TPPP/p25. These data obtained with HeLa and SH-SY5Y cells revealed the protective effect of DJ-1 against toxic SYN assemblies, which assigns a new function to the antioxidant sensor DJ-1.
format	article
author	Judit Oláh Attila Lehotzky Tibor Szénási Judit Ovádi
author_facet	Judit Oláh Attila Lehotzky Tibor Szénási Judit Ovádi
author_sort	Judit Oláh
title	Anti-Aggregative Effect of the Antioxidant DJ-1 on the TPPP/p25-Derived Pathological Associations of Alpha-Synuclein
title_short	Anti-Aggregative Effect of the Antioxidant DJ-1 on the TPPP/p25-Derived Pathological Associations of Alpha-Synuclein
title_full	Anti-Aggregative Effect of the Antioxidant DJ-1 on the TPPP/p25-Derived Pathological Associations of Alpha-Synuclein
title_fullStr	Anti-Aggregative Effect of the Antioxidant DJ-1 on the TPPP/p25-Derived Pathological Associations of Alpha-Synuclein
title_full_unstemmed	Anti-Aggregative Effect of the Antioxidant DJ-1 on the TPPP/p25-Derived Pathological Associations of Alpha-Synuclein
title_sort	anti-aggregative effect of the antioxidant dj-1 on the tppp/p25-derived pathological associations of alpha-synuclein
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/4895946aa1604e69b8204e8ea43c0786
work_keys_str_mv	AT juditolah antiaggregativeeffectoftheantioxidantdj1onthetpppp25derivedpathologicalassociationsofalphasynuclein AT attilalehotzky antiaggregativeeffectoftheantioxidantdj1onthetpppp25derivedpathologicalassociationsofalphasynuclein AT tiborszenasi antiaggregativeeffectoftheantioxidantdj1onthetpppp25derivedpathologicalassociationsofalphasynuclein AT juditovadi antiaggregativeeffectoftheantioxidantdj1onthetpppp25derivedpathologicalassociationsofalphasynuclein
_version_	1718412645553405952

Anti-Aggregative Effect of the Antioxidant DJ-1 on the TPPP/p25-Derived Pathological Associations of Alpha-Synuclein

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