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Prion‐like propagation as a pathogenic principle in frontotemporal dementia

Frontotemporal dementia is a devastating neurodegenerative disease causing stark alterations in personality and language. Characterized by severe atrophy of the frontal and temporal brain lobes, frontotemporal dementia (FTD) shows extreme heterogeneity in clinical presentation, genetic causes, and p...

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Autores principales: Hock, Eva‐Maria, Polymenidou, Magdalini
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680357/
https://www.ncbi.nlm.nih.gov/pubmed/27502124
http://dx.doi.org/10.1111/jnc.13668
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author Hock, Eva‐Maria
Polymenidou, Magdalini
author_facet Hock, Eva‐Maria
Polymenidou, Magdalini
author_sort Hock, Eva‐Maria
collection PubMed
description Frontotemporal dementia is a devastating neurodegenerative disease causing stark alterations in personality and language. Characterized by severe atrophy of the frontal and temporal brain lobes, frontotemporal dementia (FTD) shows extreme heterogeneity in clinical presentation, genetic causes, and pathological findings. Like most neurodegenerative diseases, the initial symptoms of FTD are subtle, but increase in severity over time, as the disease progresses. Clinical progression is paralleled by exacerbation of pathological findings and the involvement of broader brain regions, which currently lack mechanistic explanation. Yet, a flurry of studies indicate that protein aggregates accumulating in neurodegenerative diseases can act as propagating entities, amplifying their pathogenic conformation, in a way similar to infectious prions. In this prion‐centric view, FTD can be divided into three subtypes, TDP‐43 or FUS proteinopathy and tauopathy. Here, we review the current evidence that FTD‐linked pathology propagates in a prion‐like manner and discuss the implications of these findings for disease progression and heterogeneity. [Image: see text] Frontotemporal dementia (FTD) is a progressive neurodegenerative disease causing severe personality dysfunctions, characterized by profound heterogeneity. Accumulation of tau, TDP‐43 or FUS cytoplasmic aggregates characterize molecularly distinct and non‐overlapping FTD subtypes. Here, we discuss the current evidence suggesting that prion‐like propagation and cell‐to‐cell spread of each of these cytoplasmic aggregates may underlie disease progression and heterogeneity. This article is part of the Frontotemporal Dementia special issue.
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spelling pubmed-66803572019-08-09 Prion‐like propagation as a pathogenic principle in frontotemporal dementia Hock, Eva‐Maria Polymenidou, Magdalini J Neurochem Frontotemporal dementias: From molecular mechanisms to therapy Frontotemporal dementia is a devastating neurodegenerative disease causing stark alterations in personality and language. Characterized by severe atrophy of the frontal and temporal brain lobes, frontotemporal dementia (FTD) shows extreme heterogeneity in clinical presentation, genetic causes, and pathological findings. Like most neurodegenerative diseases, the initial symptoms of FTD are subtle, but increase in severity over time, as the disease progresses. Clinical progression is paralleled by exacerbation of pathological findings and the involvement of broader brain regions, which currently lack mechanistic explanation. Yet, a flurry of studies indicate that protein aggregates accumulating in neurodegenerative diseases can act as propagating entities, amplifying their pathogenic conformation, in a way similar to infectious prions. In this prion‐centric view, FTD can be divided into three subtypes, TDP‐43 or FUS proteinopathy and tauopathy. Here, we review the current evidence that FTD‐linked pathology propagates in a prion‐like manner and discuss the implications of these findings for disease progression and heterogeneity. [Image: see text] Frontotemporal dementia (FTD) is a progressive neurodegenerative disease causing severe personality dysfunctions, characterized by profound heterogeneity. Accumulation of tau, TDP‐43 or FUS cytoplasmic aggregates characterize molecularly distinct and non‐overlapping FTD subtypes. Here, we discuss the current evidence suggesting that prion‐like propagation and cell‐to‐cell spread of each of these cytoplasmic aggregates may underlie disease progression and heterogeneity. This article is part of the Frontotemporal Dementia special issue. John Wiley and Sons Inc. 2016-08-09 2016-08 /pmc/articles/PMC6680357/ /pubmed/27502124 http://dx.doi.org/10.1111/jnc.13668 Text en © 2016 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Frontotemporal dementias: From molecular mechanisms to therapy
Hock, Eva‐Maria
Polymenidou, Magdalini
Prion‐like propagation as a pathogenic principle in frontotemporal dementia
title Prion‐like propagation as a pathogenic principle in frontotemporal dementia
title_full Prion‐like propagation as a pathogenic principle in frontotemporal dementia
title_fullStr Prion‐like propagation as a pathogenic principle in frontotemporal dementia
title_full_unstemmed Prion‐like propagation as a pathogenic principle in frontotemporal dementia
title_short Prion‐like propagation as a pathogenic principle in frontotemporal dementia
title_sort prion‐like propagation as a pathogenic principle in frontotemporal dementia
topic Frontotemporal dementias: From molecular mechanisms to therapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680357/
https://www.ncbi.nlm.nih.gov/pubmed/27502124
http://dx.doi.org/10.1111/jnc.13668
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