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...
Guardado en:
| Autores principales: | , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
BMC
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/132f2e779abe473f8e4a5e4bfd3b76e0 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:132f2e779abe473f8e4a5e4bfd3b76e0 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:132f2e779abe473f8e4a5e4bfd3b76e02021-11-21T12:31:46Zα-Synuclein-mediated neurodegeneration in Dementia with Lewy bodies: the pathobiology of a paradox10.1186/s13578-021-00709-y2045-3701https://doaj.org/article/132f2e779abe473f8e4a5e4bfd3b76e02021-11-01T00:00:00Zhttps://doi.org/10.1186/s13578-021-00709-yhttps://doaj.org/toc/2045-3701Abstract 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.Christopher SimonTomoko SogaHirotaka James OkanoIshwar ParharBMCarticleAlzheimer’s diseaseParkinson’s diseaseBraak hypothesisOligomersFibrilsBiotechnologyTP248.13-248.65Biology (General)QH301-705.5BiochemistryQD415-436ENCell & Bioscience, Vol 11, Iss 1, Pp 1-24 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Alzheimer’s disease Parkinson’s disease Braak hypothesis Oligomers Fibrils Biotechnology TP248.13-248.65 Biology (General) QH301-705.5 Biochemistry QD415-436 |
| spellingShingle |
Alzheimer’s disease Parkinson’s disease Braak hypothesis Oligomers Fibrils Biotechnology TP248.13-248.65 Biology (General) QH301-705.5 Biochemistry QD415-436 Christopher Simon Tomoko Soga Hirotaka James Okano Ishwar Parhar α-Synuclein-mediated neurodegeneration in Dementia with Lewy bodies: the pathobiology of a paradox |
| 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. |
| format |
article |
| 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 |
| title |
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_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_sort |
α-synuclein-mediated neurodegeneration in dementia with lewy bodies: the pathobiology of a paradox |
| publisher |
BMC |
| publishDate |
2021 |
| url |
https://doaj.org/article/132f2e779abe473f8e4a5e4bfd3b76e0 |
| work_keys_str_mv |
AT christophersimon asynucleinmediatedneurodegenerationindementiawithlewybodiesthepathobiologyofaparadox AT tomokosoga asynucleinmediatedneurodegenerationindementiawithlewybodiesthepathobiologyofaparadox AT hirotakajamesokano asynucleinmediatedneurodegenerationindementiawithlewybodiesthepathobiologyofaparadox AT ishwarparhar asynucleinmediatedneurodegenerationindementiawithlewybodiesthepathobiologyofaparadox |
| _version_ |
1718418928412131328 |