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On the dynamic and even reversible nature of Leigh syndrome: Lessons from human imaging and mouse models

Leigh syndrome (LS) is a neurodegenerative disease characterized by bilaterally symmetric brainstem or basal ganglia lesions. More than 80 genes, largely impacting mitochondrial energy metabolism, can underlie LS, and no approved medicines exist. Described 70 years ago, LS was initially diagnosed by...

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Autores principales: Walker, Melissa A., Miranda, Maria, Allred, Amanda, Mootha, Vamsi K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8901530/
https://www.ncbi.nlm.nih.gov/pubmed/34656053
http://dx.doi.org/10.1016/j.conb.2021.09.006
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author Walker, Melissa A.
Miranda, Maria
Allred, Amanda
Mootha, Vamsi K.
author_facet Walker, Melissa A.
Miranda, Maria
Allred, Amanda
Mootha, Vamsi K.
author_sort Walker, Melissa A.
collection PubMed
description Leigh syndrome (LS) is a neurodegenerative disease characterized by bilaterally symmetric brainstem or basal ganglia lesions. More than 80 genes, largely impacting mitochondrial energy metabolism, can underlie LS, and no approved medicines exist. Described 70 years ago, LS was initially diagnosed by the characteristic, necrotic lesions on autopsy. It has been broadly assumed that antemortem neuroimaging abnormalities in these regions correspond to end-stage histopathology. However, clinical observations and animal studies suggest that neuroimaging findings may represent an intermediate state, that is more dynamic than previously appreciated, and even reversible. We review this literature, discuss related conditions that are treatable, and present two new LS cases with radiographic improvement. We review studies in which hypoxia reverses advanced LS in a mouse model. The fluctuating and potentially reversible nature of radiographic LS lesions will be important in clinical trial design. Better understanding of this plasticity could lead to new therapies.
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spelling pubmed-89015302022-03-08 On the dynamic and even reversible nature of Leigh syndrome: Lessons from human imaging and mouse models Walker, Melissa A. Miranda, Maria Allred, Amanda Mootha, Vamsi K. Curr Opin Neurobiol Article Leigh syndrome (LS) is a neurodegenerative disease characterized by bilaterally symmetric brainstem or basal ganglia lesions. More than 80 genes, largely impacting mitochondrial energy metabolism, can underlie LS, and no approved medicines exist. Described 70 years ago, LS was initially diagnosed by the characteristic, necrotic lesions on autopsy. It has been broadly assumed that antemortem neuroimaging abnormalities in these regions correspond to end-stage histopathology. However, clinical observations and animal studies suggest that neuroimaging findings may represent an intermediate state, that is more dynamic than previously appreciated, and even reversible. We review this literature, discuss related conditions that are treatable, and present two new LS cases with radiographic improvement. We review studies in which hypoxia reverses advanced LS in a mouse model. The fluctuating and potentially reversible nature of radiographic LS lesions will be important in clinical trial design. Better understanding of this plasticity could lead to new therapies. 2022-02 2021-10-14 /pmc/articles/PMC8901530/ /pubmed/34656053 http://dx.doi.org/10.1016/j.conb.2021.09.006 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Walker, Melissa A.
Miranda, Maria
Allred, Amanda
Mootha, Vamsi K.
On the dynamic and even reversible nature of Leigh syndrome: Lessons from human imaging and mouse models
title On the dynamic and even reversible nature of Leigh syndrome: Lessons from human imaging and mouse models
title_full On the dynamic and even reversible nature of Leigh syndrome: Lessons from human imaging and mouse models
title_fullStr On the dynamic and even reversible nature of Leigh syndrome: Lessons from human imaging and mouse models
title_full_unstemmed On the dynamic and even reversible nature of Leigh syndrome: Lessons from human imaging and mouse models
title_short On the dynamic and even reversible nature of Leigh syndrome: Lessons from human imaging and mouse models
title_sort on the dynamic and even reversible nature of leigh syndrome: lessons from human imaging and mouse models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8901530/
https://www.ncbi.nlm.nih.gov/pubmed/34656053
http://dx.doi.org/10.1016/j.conb.2021.09.006
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