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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2022
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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. |
format | Online Article Text |
id | pubmed-8901530 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
record_format | MEDLINE/PubMed |
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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