Is There a Place for Lewy Bodies before and beyond Alpha-Synuclein Accumulation? Provocative Issues in Need of Solid Explanations
In the last two decades, alpha-synuclein (alpha-syn) assumed a prominent role as a major component and seeding structure of Lewy bodies (LBs). This concept is driving ongoing research on the pathophysiology of Parkinson’s disease (PD). In line with this, alpha-syn is considered to be the guilty prot...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/7/3929 |
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| author | Paola Lenzi Gloria Lazzeri Michela Ferrucci Marco Scotto Alessandro Frati Stefano Puglisi-Allegra Carla Letizia Busceti Francesco Fornai |
| author_facet | Paola Lenzi Gloria Lazzeri Michela Ferrucci Marco Scotto Alessandro Frati Stefano Puglisi-Allegra Carla Letizia Busceti Francesco Fornai |
| author_sort | Paola Lenzi |
| collection | DOAJ |
| description | In the last two decades, alpha-synuclein (alpha-syn) assumed a prominent role as a major component and seeding structure of Lewy bodies (LBs). This concept is driving ongoing research on the pathophysiology of Parkinson’s disease (PD). In line with this, alpha-syn is considered to be the guilty protein in the disease process, and it may be targeted through precision medicine to modify disease progression. Therefore, designing specific tools to block the aggregation and spreading of alpha-syn represents a major effort in the development of disease-modifying therapies in PD. The present article analyzes concrete evidence about the significance of alpha-syn within LBs. In this effort, some dogmas are challenged. This concerns the question of whether alpha-syn is more abundant compared with other proteins within LBs. Again, the occurrence of alpha-syn compared with non-protein constituents is scrutinized. Finally, the prominent role of alpha-syn in seeding LBs as the guilty structure causing PD is questioned. These revisited concepts may be helpful in the process of validating which proteins, organelles, and pathways are likely to be involved in the damage to meso-striatal dopamine neurons and other brain regions involved in PD. |
| first_indexed | 2024-04-24T10:43:29Z |
| format | Article |
| id | doaj.art-8abc192ec03d4ee9ba49aec40284bf61 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T10:43:29Z |
| publishDate | 2024-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8abc192ec03d4ee9ba49aec40284bf612024-04-12T13:20:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-04-01257392910.3390/ijms25073929Is There a Place for Lewy Bodies before and beyond Alpha-Synuclein Accumulation? Provocative Issues in Need of Solid ExplanationsPaola Lenzi0Gloria Lazzeri1Michela Ferrucci2Marco Scotto3Alessandro Frati4Stefano Puglisi-Allegra5Carla Letizia Busceti6Francesco Fornai7Human Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyHuman Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyHuman Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyHuman Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyIRCCS—Istituto di Ricovero e Cura a Carattere Scientifico, Neuromed, 86077 Pozzili, ItalyIRCCS—Istituto di Ricovero e Cura a Carattere Scientifico, Neuromed, 86077 Pozzili, ItalyIRCCS—Istituto di Ricovero e Cura a Carattere Scientifico, Neuromed, 86077 Pozzili, ItalyHuman Anatomy, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyIn the last two decades, alpha-synuclein (alpha-syn) assumed a prominent role as a major component and seeding structure of Lewy bodies (LBs). This concept is driving ongoing research on the pathophysiology of Parkinson’s disease (PD). In line with this, alpha-syn is considered to be the guilty protein in the disease process, and it may be targeted through precision medicine to modify disease progression. Therefore, designing specific tools to block the aggregation and spreading of alpha-syn represents a major effort in the development of disease-modifying therapies in PD. The present article analyzes concrete evidence about the significance of alpha-syn within LBs. In this effort, some dogmas are challenged. This concerns the question of whether alpha-syn is more abundant compared with other proteins within LBs. Again, the occurrence of alpha-syn compared with non-protein constituents is scrutinized. Finally, the prominent role of alpha-syn in seeding LBs as the guilty structure causing PD is questioned. These revisited concepts may be helpful in the process of validating which proteins, organelles, and pathways are likely to be involved in the damage to meso-striatal dopamine neurons and other brain regions involved in PD.https://www.mdpi.com/1422-0067/25/7/3929sequestosome (p62)poly-ubiquitinphagophoreendosomemultivesicular bodiesretromer |
| spellingShingle | Paola Lenzi Gloria Lazzeri Michela Ferrucci Marco Scotto Alessandro Frati Stefano Puglisi-Allegra Carla Letizia Busceti Francesco Fornai Is There a Place for Lewy Bodies before and beyond Alpha-Synuclein Accumulation? Provocative Issues in Need of Solid Explanations International Journal of Molecular Sciences sequestosome (p62) poly-ubiquitin phagophore endosome multivesicular bodies retromer |
| title | Is There a Place for Lewy Bodies before and beyond Alpha-Synuclein Accumulation? Provocative Issues in Need of Solid Explanations |
| title_full | Is There a Place for Lewy Bodies before and beyond Alpha-Synuclein Accumulation? Provocative Issues in Need of Solid Explanations |
| title_fullStr | Is There a Place for Lewy Bodies before and beyond Alpha-Synuclein Accumulation? Provocative Issues in Need of Solid Explanations |
| title_full_unstemmed | Is There a Place for Lewy Bodies before and beyond Alpha-Synuclein Accumulation? Provocative Issues in Need of Solid Explanations |
| title_short | Is There a Place for Lewy Bodies before and beyond Alpha-Synuclein Accumulation? Provocative Issues in Need of Solid Explanations |
| title_sort | is there a place for lewy bodies before and beyond alpha synuclein accumulation provocative issues in need of solid explanations |
| topic | sequestosome (p62) poly-ubiquitin phagophore endosome multivesicular bodies retromer |
| url | https://www.mdpi.com/1422-0067/25/7/3929 |
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