@article{MTMT:34597136,
	title = {Perspective Strategies for Interventions in Parkinsonism: Remedying the Neglected Role of TPPP},
	url = {https://m2.mtmt.hu/api/publication/34597136},
	author = {Oláh, Judit and Norris, Vic and Lehotzky, Attila and Ovádi, Judit},
	doi = {10.3390/cells13040338},
	journal-iso = {CELLS-BASEL},
	journal = {CELLS},
	volume = {13},
	unique-id = {34597136},
	abstract = {Neurological disorders such as Parkinsonism cause serious socio-economic problems as there are, at present, only therapies that treat their symptoms. The well-established hallmark alpha-synuclein (SYN) is enriched in the inclusion bodies characteristic of Parkinsonism. We discovered a prominent partner of SYN, termed Tubulin Polymerization Promoting Protein (TPPP), which has important physiological and pathological activities such as the regulation of the microtubule network and the promotion of SYN aggregation. The role of TPPP in Parkinsonism is often neglected in research, which we here attempt to remedy. In the normal brain, SYN and TPPP are expressed endogenously in neurons and oligodendrocytes, respectively, whilst, at an early stage of Parkinsonism, soluble hetero-associations of these proteins are found in both cell types. The cell-to-cell transmission of these proteins, which is central to disease progression, provides a unique situation for specific drug targeting. Different strategies for intervention and for the discovery of biomarkers include (i) interface targeting of the SYN-TPPP hetero-complex; (ii) proteolytic degradation of SYN and/or TPPP using the PROTAC technology; and (iii) depletion of the proteins by miRNA technology. We also discuss the potential roles of SYN and TPPP in the phenotype stabilization of neurons and oligodendrocytes.},
	year = {2024},
	eissn = {2073-4409},
	orcid-numbers = {Norris, Vic/0000-0002-1725-7262}
}

@article{MTMT:34061155,
	title = {The Sherpa hypothesis: Phenotype-Preserving Disordered Proteins stabilize the phenotypes of neurons and oligodendrocytes},
	url = {https://m2.mtmt.hu/api/publication/34061155},
	author = {Norris, Vic and Oláh, Judit and Krylov, Sergey N. and Uversky, Vladimir N. and Ovádi, Judit},
	doi = {10.1038/s41540-023-00291-8},
	journal-iso = {NPJ SYST BIOL APPL},
	journal = {NPJ SYSTEMS BIOLOGY AND APPLICATIONS},
	volume = {9},
	unique-id = {34061155},
	abstract = {Intrinsically disordered proteins (IDPs), which can interact with many partner proteins, are central to many physiological functions and to various pathologies that include neurodegeneration. Here, we introduce the Sherpa hypothesis, according to which a subset of stable IDPs that we term Phenotype-Preserving Disordered Proteins (PPDP) play a central role in protecting cell phenotypes from perturbations. To illustrate and test this hypothesis, we computer-simulate some salient features of how cells evolve and differentiate in the presence of either a single PPDP or two incompatible PPDPs. We relate this virtual experiment to the pathological interactions between two PPDPs, α-synuclein and Tubulin Polymerization Promoting Protein/p25, in neurodegenerative disorders. Finally, we discuss the implications of the Sherpa hypothesis for aptamer-based therapies of such disorders.},
	year = {2023},
	eissn = {2056-7189},
	orcid-numbers = {Norris, Vic/0000-0002-1725-7262; Uversky, Vladimir N./0000-0002-4037-5857}
}

@article{MTMT:33163273,
	title = {Modulatory Role of TPPP3 in Microtubule Organization and Its Impact on Alpha-Synuclein Pathology.},
	url = {https://m2.mtmt.hu/api/publication/33163273},
	author = {Oláh, Judit and Lehotzky, Attila and Szénási, Tibor and Berki, Tímea and Ovádi, Judit},
	doi = {10.3390/cells11193025},
	journal-iso = {CELLS-BASEL},
	journal = {CELLS},
	volume = {11},
	unique-id = {33163273},
	abstract = {Parkinson's disease is characterized by locomotion deficits, dopaminergic neuronal loss and alpha-synuclein (SYN) aggregates; the Tubulin Polymerization Promoting Protein (TPPP/p25 or TPPP1) is also implicated in these processes. The moonlighting and chameleon TPPP1 modulates the dynamics/stability of the multifunctional microtubule network by promoting its acetylation and bundling. Previously, we identified the microtubule-associated TPPP3, a homologue of TPPP1 lacking its N-terminus; however, its involvement in physiological or pathological processes was not elucidated. In this work, we have shown the modulatory role of TPPP3, similarly to TPPP1, in microtubule organization, as well as its homo- and hetero-associations with TPPP1. TPPP3, in contrast to TPPP1, virtually does not bind to SYN; consequently, it does not promote SYN aggregation. Its anti-aggregative potency is achieved by counteracting the formation of the TPPP1-SYN pathological complex/aggregation leading to Parkinsonism. The interactions of TPPP3 have been determined and quantified in vitro with recombinant human proteins, cell extracts and in living human cells using different methods including bifunctional fluorescence complementation. The tight association of TPPP3 with TPPP1, but not with SYN, may ensure a unique mechanism for its inhibitory effect. TPPP3 or its selected fragments may become a leading agent for developing anti-Parkinson agents.},
	keywords = {Brain; PARKINSONISM; ALPHA-SYNUCLEIN; PATHOPHYSIOLOGY; Microtubule; TPPP proteins},
	year = {2022},
	eissn = {2073-4409},
	orcid-numbers = {Szénási, Tibor/0000-0002-8405-0798; Berki, Tímea/0000-0002-0134-8127}
}

@article{MTMT:32661321,
	title = {Challenges in Discovering Drugs That Target the Protein–Protein Interactions of Disordered Proteins},
	url = {https://m2.mtmt.hu/api/publication/32661321},
	author = {Oláh, Judit and Szénási, Tibor and Lehotzky, Attila and Norris, Victor and Ovádi, Judit},
	doi = {10.3390/ijms23031550},
	journal-iso = {INT J MOL SCI},
	journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES},
	volume = {23},
	unique-id = {32661321},
	issn = {1661-6596},
	year = {2022},
	eissn = {1422-0067},
	orcid-numbers = {Szénási, Tibor/0000-0002-8405-0798; Norris, Victor/0000-0002-1725-7262}
}

@{MTMT:31897147,
	title = {A potential innovative therapy for Parkinson’s disease: Selective destruction of the pathological assemblies of alpha-synuclein},
	url = {https://m2.mtmt.hu/api/publication/31897147},
	author = {Oláh, Judit and Lehotzky, Attila and Szénási, Tibor and Ovádi, Judit},
	booktitle = {Dementia in Parkinson's Disease},
	doi = {10.5772/intechopen.97271},
	unique-id = {31897147},
	year = {2022},
	orcid-numbers = {Szénási, Tibor/0000-0002-8405-0798}
}

@article{MTMT:32477494,
	title = {Anti-aggregative effect of the antioxidant dj-1 on the tppp/p25-derived pathological associations of alpha-synuclein},
	url = {https://m2.mtmt.hu/api/publication/32477494},
	author = {Oláh, Judit and Lehotzky, Attila and Szénási, Tibor and Ovádi, Judit},
	doi = {10.3390/cells10112909},
	journal-iso = {CELLS-BASEL},
	journal = {CELLS},
	volume = {10},
	unique-id = {32477494},
	abstract = {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.},
	keywords = {PARKINSONISM; ALPHA-SYNUCLEIN; TPPP/P25; DJ-1; BiFC; Anti-aggregative effect},
	year = {2021},
	eissn = {2073-4409},
	orcid-numbers = {Szénási, Tibor/0000-0002-8405-0798}
}

@article{MTMT:32132687,
	title = {Role of Multifunctional Cytoskeletal Filaments in Coronaviridae Infections: Therapeutic Opportunities for COVID-19 in a Nutshell},
	url = {https://m2.mtmt.hu/api/publication/32132687},
	author = {Norris, Victor and Ovádi, Judit},
	doi = {10.3390/cells10071818},
	journal-iso = {CELLS-BASEL},
	journal = {CELLS},
	volume = {10},
	unique-id = {32132687},
	year = {2021},
	eissn = {2073-4409}
}

@article{MTMT:32061631,
	title = {Co-Transmission of Alpha-Synuclein and TPPP/p25 Inhibits Their Proteolytic Degradation in Human Cell Models},
	url = {https://m2.mtmt.hu/api/publication/32061631},
	author = {Lehotzky, Attila and Oláh, Judit and Fekete, János Tibor and Szénási, Tibor and Szabó, Edit Zsuzsanna and Győrffy, Balázs and Várady, György and Ovádi, Judit},
	doi = {10.3389/fmolb.2021.666026},
	journal-iso = {FRONT MOL BIOSCI},
	journal = {FRONTIERS IN MOLECULAR BIOSCIENCES},
	volume = {8},
	unique-id = {32061631},
	year = {2021},
	eissn = {2296-889X},
	orcid-numbers = {Fekete, János Tibor/0000-0002-6672-6563; Szénási, Tibor/0000-0002-8405-0798; Győrffy, Balázs/0000-0002-5772-3766; Várady, György/0000-0003-2012-9680}
}

@article{MTMT:31400077,
	title = {HaloTag-targeted Sirtuin rearranging ligand (SirReal) for the development of proteolysis targeting chimeras (PROTACs) against the lysine deacetylase Sirtuin 2 (Sirt2).},
	url = {https://m2.mtmt.hu/api/publication/31400077},
	author = {Schiedel, Matthias and Lehotzky, Attila and Szunyogh, Sandor and Oláh, Judit and Hammelmann, Sören and Wössner, Nathalie and Robaa, Dina and Einsle, Oliver and Sippl, Wolfgang and Ovádi, Judit and Jung, Manfred},
	doi = {10.1002/cbic.202000351},
	journal-iso = {CHEMBIOCHEM},
	journal = {CHEMBIOCHEM},
	volume = {21},
	unique-id = {31400077},
	issn = {1439-4227},
	abstract = {We have discovered the sirtuin rearranging ligands (SirReals) as a novel class of highly potent and selective inhibitors of the NAD+-dependent lysine deacetylase sirtuin 2 (Sirt2). In previous studies, conjugation of a SirReal with a ligand for the E3 ubiquitin ligase cereblon to form a so-called proteolysis targeting chimera (PROTAC), enabled small molecule-induced degradation of Sirt2. Here, we report the structure-based development of a chloroalkylated SirReal that induces the degradation of Sirt2 mediated by Halo-tagged E3 ubiquitin ligases. Using this orthogonal approach for Sirt2 degradation, we show that also other E3 ligases than cereblon, such as the E3 ubiquitin ligase parkin, can be harnessed for small molecule-induced Sirt2 degradation, thereby emphasizing the great potential of parkin to be utilized as an E3 ligase for new PROTACs approaches. Thus, our study provides new insights into targeted protein degradation in general and Sirt2 degradation in particular.},
	keywords = {SIRTUINS; tubulin; epigenetics; HaloTag; PROTACs},
	year = {2020},
	eissn = {1439-7633},
	pages = {3371-3376}
}

@article{MTMT:31177407,
	title = {Microtubule-Associated Proteins with Regulatory Functions by Day and Pathological Potency at Night.},
	url = {https://m2.mtmt.hu/api/publication/31177407},
	author = {Oláh, Judit and Lehotzky, Attila and Szunyogh, Sándor and Szénási, Tibor and Orosz, Ferenc and Ovádi, Judit},
	doi = {10.3390/cells9020357},
	journal-iso = {CELLS-BASEL},
	journal = {CELLS},
	volume = {9},
	unique-id = {31177407},
	abstract = {The sensing, integrating, and coordinating features of the eukaryotic cells are achieved by the complex ultrastructural arrays and multifarious functions of the cytoskeleton, including the microtubule network. Microtubules play crucial roles achieved by their decoration with proteins/enzymes as well as by posttranslational modifications. This review focuses on the Tubulin Polymerization Promoting Protein (TPPP/p25), a new microtubule associated protein, on its "regulatory functions by day and pathological functions at night". Physiologically, the moonlighting TPPP/p25 modulates the dynamics and stability of the microtubule network by bundling microtubules and enhancing the tubulin acetylation due to the inhibition of tubulin deacetylases. The optimal endogenous TPPP/p25 level is crucial for its physiological functions, to the differentiation of oligodendrocytes, which are the major constituents of the myelin sheath. Pathologically, TPPP/p25 forms toxic oligomers/aggregates with α-synuclein in neurons and oligodendrocytes in Parkinson's disease and Multiple System Atrophy, respectively; and their complex is a potential therapeutic drug target. TPPP/p25-derived microtubule hyperacetylation counteracts uncontrolled cell division. All these issues reveal the anti-mitotic and α-synuclein aggregation-promoting potency of TPPP/p25, consistent with the finding that Parkinson's disease patients have reduced risk for certain cancers.},
	keywords = {CANCER; Parkinson's disease; Drug target; Inclusion; mitosis inhibition; tubulin acetylation; TPPP; microtubule ultrastructure},
	year = {2020},
	eissn = {2073-4409},
	orcid-numbers = {Szénási, Tibor/0000-0002-8405-0798; Orosz, Ferenc/0000-0003-3169-0078}
}