On the dynamic and even reversible nature of Leigh syndrome: Lessons from human imaging and mouse models.
Journal
Current opinion in neurobiology
ISSN: 1873-6882
Titre abrégé: Curr Opin Neurobiol
Pays: England
ID NLM: 9111376
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
03
06
2021
revised:
01
08
2021
accepted:
07
09
2021
pubmed:
17
10
2021
medline:
2
4
2022
entrez:
16
10
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34656053
pii: S0959-4388(21)00107-0
doi: 10.1016/j.conb.2021.09.006
pmc: PMC8901530
mid: NIHMS1771536
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
80-90Subventions
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NINDS NIH HHS
ID : K08 NS117889
Pays : United States
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: VKM is listed as a coinventor on a patent on the therapeutic uses of hypoxia for mitochondrial diseases. VKM is on the Scientific Advisory Board of 5am Ventures and Janssen Pharmaceuticals.
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