Clinical application of prion-like seeding in α-synucleinopathies: Early and non-invasive diagnosis and therapeutic development
The accumulation and deposition of misfolded α-synuclein (α-Syn) aggregates in the brain is the central event in the pathogenesis of α-synucleinopathies, including Parkinson’s disease, dementia with Lewy bodies, and multiple-system atrophy. Currently, the diagnosis of these diseases mainly relies on...
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Published in | Frontiers in molecular neuroscience Vol. 15; p. 975619 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Lausanne
Frontiers Research Foundation
10.10.2022
Frontiers Media S.A |
Subjects | |
Online Access | Get full text |
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Summary: | The accumulation and deposition of misfolded α-synuclein (α-Syn) aggregates in the brain is the central event in the pathogenesis of α-synucleinopathies, including Parkinson’s disease, dementia with Lewy bodies, and multiple-system atrophy. Currently, the diagnosis of these diseases mainly relies on the recognition of advanced clinical manifestations. Differential diagnosis among the various α-synucleinopathies subtypes remains challenging. Misfolded α-Syn can template its native counterpart into the same misfolded one within or between cells, behaving as a prion-like seeding. Protein-misfolding cyclic amplification and real-time quaking-induced conversion are ultrasensitive protein amplification assays initially used for the detection of prion diseases. Both assays showed high sensitivity and specificity in detection of α-synucleinopathies even in the pre-clinical stage recently. Herein, we collectively reviewed the prion-like properties of α-Syn and critically assessed the detection techniques of α-Syn-seeding activity. The progress of test tissues, which tend to be less invasive, is presented, particularly nasal swab, which is now widely known owing to the global fight against coronavirus disease 2019. We highlight the clinical application of α-Syn seeding in early and non-invasive diagnosis. Moreover, some promising therapeutic perspectives and clinical trials targeting α-Syn-seeding mechanisms are presented. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 Edited by: Ayse Ulusoy, Helmholtz Association of German Research Centers (HZ), Germany Reviewed by: Bulent Elibol, Hacettepe University Hospital, Turkey; Silvia Cerri, National Neurological Institute, Italy These authors have contributed equally to this work This article was submitted to Brain Disease Mechanisms, a section of the journal Frontiers in Molecular Neuroscience |
ISSN: | 1662-5099 1662-5099 |
DOI: | 10.3389/fnmol.2022.975619 |