Disorders of synaptic vesicle fusion machinery

Holly Melland, Elysa M. Carr, Sarah L. Gordon

Research output: Contribution to journalReview ArticleResearchpeer-review

39 Citations (Scopus)


The revolution in genetic technology has ushered in a new age for our understanding of the underlying causes of neurodevelopmental, neuromuscular and neurodegenerative disorders, revealing that the presynaptic machinery governing synaptic vesicle fusion is compromised in many of these neurological disorders. This builds upon decades of research showing that disturbance to neurotransmitter release via toxins can cause acute neurological dysfunction. In this review, we focus on disorders of synaptic vesicle fusion caused either by toxic insult to the presynapse or alterations to genes encoding the key proteins that control and regulate fusion: the SNARE proteins (synaptobrevin, syntaxin-1 and SNAP-25), Munc18, Munc13, synaptotagmin, complexin, CSPα, α-synuclein, PRRT2 and tomosyn. We discuss the roles of these proteins and the cellular and molecular mechanisms underpinning neurological deficits in these disorders. (Figure presented.).

Original languageEnglish
Pages (from-to)130-164
Number of pages35
JournalJournal of Neurochemistry
Issue number2
Publication statusPublished - Apr 2021
Externally publishedYes


  • epilepsy
  • exocytosis
  • intellectual disability
  • movement disorder
  • neurodegeneration
  • neurotoxin

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