Perspective Strategies for Interventions in Parkinsonism: Remedying the Neglected Role of TPPP
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 part...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/13/4/338 |
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| author | Judit Oláh Vic Norris Attila Lehotzky Judit Ovádi |
| author_facet | Judit Oláh Vic Norris Attila Lehotzky Judit Ovádi |
| author_sort | Judit Oláh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T22:37:45Z |
| format | Article |
| id | doaj.art-87252d63408c4344882cf1ea7f258245 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-07T22:37:45Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-87252d63408c4344882cf1ea7f2582452024-02-23T15:11:56ZengMDPI AGCells2073-44092024-02-0113433810.3390/cells13040338Perspective Strategies for Interventions in Parkinsonism: Remedying the Neglected Role of TPPPJudit Oláh0Vic Norris1Attila Lehotzky2Judit Ovádi3Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, H-1117 Budapest, HungaryLaboratory of Bacterial Communication and Anti-Infection Strategies, EA 4312, University of Rouen, 76821 Mont Saint Aignan, FranceInstitute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, H-1117 Budapest, HungaryInstitute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, H-1117 Budapest, HungaryNeurological 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.https://www.mdpi.com/2073-4409/13/4/338Parkinsonismmethodologiesalpha-synucleinTPPPdrug targeting |
| spellingShingle | Judit Oláh Vic Norris Attila Lehotzky Judit Ovádi Perspective Strategies for Interventions in Parkinsonism: Remedying the Neglected Role of TPPP Cells Parkinsonism methodologies alpha-synuclein TPPP drug targeting |
| title | Perspective Strategies for Interventions in Parkinsonism: Remedying the Neglected Role of TPPP |
| title_full | Perspective Strategies for Interventions in Parkinsonism: Remedying the Neglected Role of TPPP |
| title_fullStr | Perspective Strategies for Interventions in Parkinsonism: Remedying the Neglected Role of TPPP |
| title_full_unstemmed | Perspective Strategies for Interventions in Parkinsonism: Remedying the Neglected Role of TPPP |
| title_short | Perspective Strategies for Interventions in Parkinsonism: Remedying the Neglected Role of TPPP |
| title_sort | perspective strategies for interventions in parkinsonism remedying the neglected role of tppp |
| topic | Parkinsonism methodologies alpha-synuclein TPPP drug targeting |
| url | https://www.mdpi.com/2073-4409/13/4/338 |
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