α-Synuclein-mediated neurodegeneration in Dementia with Lewy bodies: the pathobiology of a paradox
Abstract Dementia with Lewy bodies (DLB) is epitomized by the pathognomonic manifestation of α-synuclein-laden Lewy bodies within selectively vulnerable neurons in the brain. By virtue of prion-like inheritance, the α-synuclein protein inexorably undergoes extensive conformational metamorphoses and...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-11-01
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| Series: | Cell & Bioscience |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13578-021-00709-y |
| _version_ | 1818995915684315136 |
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| author | Christopher Simon Tomoko Soga Hirotaka James Okano Ishwar Parhar |
| author_facet | Christopher Simon Tomoko Soga Hirotaka James Okano Ishwar Parhar |
| author_sort | Christopher Simon |
| collection | DOAJ |
| description | Abstract Dementia with Lewy bodies (DLB) is epitomized by the pathognomonic manifestation of α-synuclein-laden Lewy bodies within selectively vulnerable neurons in the brain. By virtue of prion-like inheritance, the α-synuclein protein inexorably undergoes extensive conformational metamorphoses and culminate in the form of fibrillar polymorphs, instigating calamitous damage to the brain’s neuropsychological networks. This epiphenomenon is nebulous, however, by lingering uncertainty over the quasi “pathogenic” behavior of α-synuclein conformers in DLB pathobiology. Despite numerous attempts, a monolithic “α-synuclein” paradigm that is able to untangle the enigma enshrouding the clinicopathological spectrum of DLB has failed to emanate. In this article, we review conceptual frameworks of α-synuclein dependent cell-autonomous and non-autonomous mechanisms that are likely to facilitate the transneuronal spread of degeneration through the neuraxis. In particular, we describe how the progressive demise of susceptible neurons may evolve from cellular derangements perpetrated by α-synuclein misfolding and aggregation. Where pertinent, we show how these bona fide mechanisms may mutually accentuate α-synuclein-mediated neurodegeneration in the DLB brain. |
| first_indexed | 2024-12-20T21:21:26Z |
| format | Article |
| id | doaj.art-132f2e779abe473f8e4a5e4bfd3b76e0 |
| institution | Directory Open Access Journal |
| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-12-20T21:21:26Z |
| publishDate | 2021-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj.art-132f2e779abe473f8e4a5e4bfd3b76e02022-12-21T19:26:17ZengBMCCell & Bioscience2045-37012021-11-0111112410.1186/s13578-021-00709-yα-Synuclein-mediated neurodegeneration in Dementia with Lewy bodies: the pathobiology of a paradoxChristopher Simon0Tomoko Soga1Hirotaka James Okano2Ishwar Parhar3Brain Research Institute, Jeffrey Cheah School of Medicine and Health Sciences, Monash University MalaysiaBrain Research Institute, Jeffrey Cheah School of Medicine and Health Sciences, Monash University MalaysiaDivision of Regenerative Medicine, Research Center for Medical Sciences, The Jikei University School of MedicineBrain Research Institute, Jeffrey Cheah School of Medicine and Health Sciences, Monash University MalaysiaAbstract Dementia with Lewy bodies (DLB) is epitomized by the pathognomonic manifestation of α-synuclein-laden Lewy bodies within selectively vulnerable neurons in the brain. By virtue of prion-like inheritance, the α-synuclein protein inexorably undergoes extensive conformational metamorphoses and culminate in the form of fibrillar polymorphs, instigating calamitous damage to the brain’s neuropsychological networks. This epiphenomenon is nebulous, however, by lingering uncertainty over the quasi “pathogenic” behavior of α-synuclein conformers in DLB pathobiology. Despite numerous attempts, a monolithic “α-synuclein” paradigm that is able to untangle the enigma enshrouding the clinicopathological spectrum of DLB has failed to emanate. In this article, we review conceptual frameworks of α-synuclein dependent cell-autonomous and non-autonomous mechanisms that are likely to facilitate the transneuronal spread of degeneration through the neuraxis. In particular, we describe how the progressive demise of susceptible neurons may evolve from cellular derangements perpetrated by α-synuclein misfolding and aggregation. Where pertinent, we show how these bona fide mechanisms may mutually accentuate α-synuclein-mediated neurodegeneration in the DLB brain.https://doi.org/10.1186/s13578-021-00709-yAlzheimer’s diseaseParkinson’s diseaseBraak hypothesisOligomersFibrils |
| spellingShingle | Christopher Simon Tomoko Soga Hirotaka James Okano Ishwar Parhar α-Synuclein-mediated neurodegeneration in Dementia with Lewy bodies: the pathobiology of a paradox Cell & Bioscience Alzheimer’s disease Parkinson’s disease Braak hypothesis Oligomers Fibrils |
| title | α-Synuclein-mediated neurodegeneration in Dementia with Lewy bodies: the pathobiology of a paradox |
| title_full | α-Synuclein-mediated neurodegeneration in Dementia with Lewy bodies: the pathobiology of a paradox |
| title_fullStr | α-Synuclein-mediated neurodegeneration in Dementia with Lewy bodies: the pathobiology of a paradox |
| title_full_unstemmed | α-Synuclein-mediated neurodegeneration in Dementia with Lewy bodies: the pathobiology of a paradox |
| title_short | α-Synuclein-mediated neurodegeneration in Dementia with Lewy bodies: the pathobiology of a paradox |
| title_sort | α synuclein mediated neurodegeneration in dementia with lewy bodies the pathobiology of a paradox |
| topic | Alzheimer’s disease Parkinson’s disease Braak hypothesis Oligomers Fibrils |
| url | https://doi.org/10.1186/s13578-021-00709-y |
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