Anti-aggregative effect of the antioxidant dj-1 on the tppp/p25-derived pathological associations of alpha-synuclein

Oláh, Judit and Lehotzky, Attila and Szénási, Tibor and Ovádi, Judit (2021) Anti-aggregative effect of the antioxidant dj-1 on the tppp/p25-derived pathological associations of alpha-synuclein. CELLS, 10 (11). ISSN 2073-4409

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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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Item Type: Article
Additional Information: Export Date: 4 November 2021 Correspondence Address: Oláh, J.; Cell Architecture Lab, Hungary; email: Correspondence Address: Ovádi, J.; Cell Architecture Lab, Hungary; email: Funding details: Hungarian Scientific Research Fund, OTKA, PD-124061 Funding details: Magyar Tudományos Akadémia, MTA, BO/340/19 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH Funding text 1: Funding: This work was funded by the Hungarian National Research, Development and Innovation Office Grants OTKA [PD-124061] to T. Szénási, and by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences [BO/340/19] to J.O. (Judit Oláh).
Uncontrolled Keywords: PARKINSONISM; ALPHA-SYNUCLEIN; TPPP/P25; DJ-1; BiFC; Anti-aggregative effect;
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3015 Molecular biology / molekuláris biológia
Q Science / természettudomány > QR Microbiology / mikrobiológia
Depositing User: MTMT SWORD
Date Deposited: 14 Sep 2022 16:54
Last Modified: 14 Sep 2022 16:54

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