Revisiting the role of mitochondria in spinal muscular atrophy

Rachel James, Helena Chaytow, Leire Ledahawsky, Thomas H Gillingwater

Research output: Contribution to journalReview articlepeer-review

Abstract / Description of output

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease of variable clinical severity that is caused by mutations in the survival motor neuron 1 (SMN1) gene. Despite its name, SMN is a ubiquitous protein that functions within and outside the nervous system and has multiple cellular roles in transcription, translation, and proteostatic mechanisms. Encouragingly, several SMN-directed therapies have recently reached the clinic, albeit this has highlighted the increasing need to develop combinatorial therapies for SMA to achieve full clinical efficacy. As a subcellular site of dysfunction in SMA, mitochondria represents a relevant target for a combinatorial therapy. Accordingly, we will discuss our current understanding of mitochondrial dysfunction in SMA, highlighting mitochondrial-based pathways that offer further mechanistic insights into the involvement of mitochondria in SMA. This may ultimately facilitate translational development of targeted mitochondrial therapies for SMA. Due to clinical and mechanistic overlaps, such strategies may also benefit other motor neuron diseases and related neurodegenerative disorders.
Original languageEnglish
Pages (from-to)4785-4804
Number of pages20
JournalCellular and Molecular Life Sciences
Publication statusPublished - 5 Apr 2021

Keywords / Materials (for Non-textual outputs)

  • survival motor neuron
  • mitochondrial dysfunction
  • mitophagy
  • combinatorial therapy
  • motor neuron disease
  • neurodegenerative disorders


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