Mitochondrial Dynamics in the Neonatal Brain -a potential target following injury?

Jones, Adam; Thornton, Claire

Abstract

The impact of birth asphyxia and its sequelae, hypoxic-ischaemic brain injury, is long lasting and significant, both for the infant and for their family. Treatment options are limited to therapeutic hypothermia, which is not universally successful and is unavailable in low resource settings. The energy deficits that accompany neuronal death following interruption of blood flow to the brain implicate mitochondrial dysfunction. Such hypoxic-ischaemic insults trigger mitochondrial outer membrane permeabilisation leading to release of pro-apoptotic proteins into the cytosol and cell death. More recently, key players in mitochondrial fission and fusion have been identified as targets following hypoxic-ischaemic brain injury. This review aims to provide an introduction to the molecular players and pathways driving mitochondrial dynamics, the regulation of these pathways and how they are altered following hypoxic-ischaemic insult. Finally, we review progress on repurposing or repositioning drugs already approved for other indications, which may target mitochondrial dynamics and provide promising avenues for intervention following brain injury. Such repurposing may provide a mechanism to fast-track low cost treatment options to the clinic.

Citation

Jones, A., & Thornton, C. (2022). Mitochondrial Dynamics in the Neonatal Brain -a potential target following injury?. Bioscience Reports, https://doi.org/10.1042/BSR20211696

• Journal Article Type: Review
• Acceptance Date: Mar 11, 2022
• Publication Date: Mar 23, 2022
• Deposit Date: Jan 31, 2022
• Publicly Available Date: Jul 14, 2022
• Journal: Bioscience Reports
• Print ISSN: 0144-8463
• Electronic ISSN: 1573-4935
• Publisher: Portland Press
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1042/BSR20211696
• Additional Information: Sorry that this didn't get to you before submission but the deadline was this evening.