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Hunting for the cause: Evidence for prion-like mechanisms in Huntington’s disease

The hypothesis that pathogenic protein aggregates associated with neurodegenerative diseases spread from cell-to-cell in the brain in a manner akin to infectious prions has gained substantial momentum due to an explosion of research in the past 10–15 years. Here, we review current evidence supportin...

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Autores principales: Donnelly, Kirby M., Coleman, Cevannah M., Fuller, Madison L., Reed, Victoria L., Smerina, Dayna, Tomlinson, David S., Pearce, Margaret M. Panning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9448931/
https://www.ncbi.nlm.nih.gov/pubmed/36090278
http://dx.doi.org/10.3389/fnins.2022.946822
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author Donnelly, Kirby M.
Coleman, Cevannah M.
Fuller, Madison L.
Reed, Victoria L.
Smerina, Dayna
Tomlinson, David S.
Pearce, Margaret M. Panning
author_facet Donnelly, Kirby M.
Coleman, Cevannah M.
Fuller, Madison L.
Reed, Victoria L.
Smerina, Dayna
Tomlinson, David S.
Pearce, Margaret M. Panning
author_sort Donnelly, Kirby M.
collection PubMed
description The hypothesis that pathogenic protein aggregates associated with neurodegenerative diseases spread from cell-to-cell in the brain in a manner akin to infectious prions has gained substantial momentum due to an explosion of research in the past 10–15 years. Here, we review current evidence supporting the existence of prion-like mechanisms in Huntington’s disease (HD), an autosomal dominant neurodegenerative disease caused by expansion of a CAG repeat tract in exon 1 of the huntingtin (HTT) gene. We summarize information gained from human studies and in vivo and in vitro models of HD that strongly support prion-like features of the mutant HTT (mHTT) protein, including potential involvement of molecular features of mHTT seeds, synaptic structures and connectivity, endocytic and exocytic mechanisms, tunneling nanotubes, and nonneuronal cells in mHTT propagation in the brain. We discuss mechanisms by which mHTT aggregate spreading and neurotoxicity could be causally linked and the potential benefits of targeting prion-like mechanisms in the search for new disease-modifying therapies for HD and other fatal neurodegenerative diseases.
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spelling pubmed-94489312022-09-08 Hunting for the cause: Evidence for prion-like mechanisms in Huntington’s disease Donnelly, Kirby M. Coleman, Cevannah M. Fuller, Madison L. Reed, Victoria L. Smerina, Dayna Tomlinson, David S. Pearce, Margaret M. Panning Front Neurosci Neuroscience The hypothesis that pathogenic protein aggregates associated with neurodegenerative diseases spread from cell-to-cell in the brain in a manner akin to infectious prions has gained substantial momentum due to an explosion of research in the past 10–15 years. Here, we review current evidence supporting the existence of prion-like mechanisms in Huntington’s disease (HD), an autosomal dominant neurodegenerative disease caused by expansion of a CAG repeat tract in exon 1 of the huntingtin (HTT) gene. We summarize information gained from human studies and in vivo and in vitro models of HD that strongly support prion-like features of the mutant HTT (mHTT) protein, including potential involvement of molecular features of mHTT seeds, synaptic structures and connectivity, endocytic and exocytic mechanisms, tunneling nanotubes, and nonneuronal cells in mHTT propagation in the brain. We discuss mechanisms by which mHTT aggregate spreading and neurotoxicity could be causally linked and the potential benefits of targeting prion-like mechanisms in the search for new disease-modifying therapies for HD and other fatal neurodegenerative diseases. Frontiers Media S.A. 2022-08-24 /pmc/articles/PMC9448931/ /pubmed/36090278 http://dx.doi.org/10.3389/fnins.2022.946822 Text en Copyright © 2022 Donnelly, Coleman, Fuller, Reed, Smerina, Tomlinson and Pearce. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Donnelly, Kirby M.
Coleman, Cevannah M.
Fuller, Madison L.
Reed, Victoria L.
Smerina, Dayna
Tomlinson, David S.
Pearce, Margaret M. Panning
Hunting for the cause: Evidence for prion-like mechanisms in Huntington’s disease
title Hunting for the cause: Evidence for prion-like mechanisms in Huntington’s disease
title_full Hunting for the cause: Evidence for prion-like mechanisms in Huntington’s disease
title_fullStr Hunting for the cause: Evidence for prion-like mechanisms in Huntington’s disease
title_full_unstemmed Hunting for the cause: Evidence for prion-like mechanisms in Huntington’s disease
title_short Hunting for the cause: Evidence for prion-like mechanisms in Huntington’s disease
title_sort hunting for the cause: evidence for prion-like mechanisms in huntington’s disease
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9448931/
https://www.ncbi.nlm.nih.gov/pubmed/36090278
http://dx.doi.org/10.3389/fnins.2022.946822
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