1. Disorders of synaptic vesicle fusion machinery
- Author
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Holly Melland, Sarah L Gordon, and Elysa Carr
- Subjects
0301 basic medicine ,Synaptobrevin ,Biology ,Neurotransmission ,Membrane Fusion ,Synaptic Transmission ,Biochemistry ,Synaptic vesicle ,Exocytosis ,Presynapse ,Synaptotagmin 1 ,Synaptotagmins ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,0302 clinical medicine ,Complexin ,medicine ,Animals ,Humans ,Neurons ,Alpha-synuclein ,Neurodegeneration ,medicine.disease ,030104 developmental biology ,chemistry ,Synaptic Vesicles ,Neuroscience ,030217 neurology & neurosurgery - Abstract
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.
- Published
- 2020