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Neurological Phenotypes in Mouse Models of Mitochondrial Disease and Relevance to Human Neuropathology.

Authors :
Olkhova, Elizaveta A.
Smith, Laura A.
Bradshaw, Carla
Gorman, GrĂ¡inne S.
Erskine, Daniel
Ng, Yi Shiau
Source :
International Journal of Molecular Sciences; Jun2023, Vol. 24 Issue 11, p9698, 21p
Publication Year :
2023

Abstract

Mitochondrial diseases represent the most common inherited neurometabolic disorders, for which no effective therapy currently exists for most patients. The unmet clinical need requires a more comprehensive understanding of the disease mechanisms and the development of reliable and robust in vivo models that accurately recapitulate human disease. This review aims to summarise and discuss various mouse models harbouring transgenic impairments in genes that regulate mitochondrial function, specifically their neurological phenotype and neuropathological features. Ataxia secondary to cerebellar impairment is one of the most prevalent neurological features of mouse models of mitochondrial dysfunction, consistent with the observation that progressive cerebellar ataxia is a common neurological manifestation in patients with mitochondrial disease. The loss of Purkinje neurons is a shared neuropathological finding in human post-mortem tissues and numerous mouse models. However, none of the existing mouse models recapitulate other devastating neurological phenotypes, such as refractory focal seizures and stroke-like episodes seen in patients. Additionally, we discuss the roles of reactive astrogliosis and microglial reactivity, which may be driving the neuropathology in some of the mouse models of mitochondrial dysfunction, as well as mechanisms through which cellular death may occur, beyond apoptosis, in neurons undergoing mitochondrial bioenergy crisis. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16616596
Volume :
24
Issue :
11
Database :
Complementary Index
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
164218614
Full Text :
https://doi.org/10.3390/ijms24119698