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Review
. 2021 Apr;157(2):130-164.
doi: 10.1111/jnc.15181. Epub 2020 Oct 4.

Disorders of synaptic vesicle fusion machinery

Holly Melland  1 , Elyas H Arvell  1 , Sarah L Gordon  1
Affiliations
Review

Disorders of synaptic vesicle fusion machinery

Holly Melland et al. J Neurochem. 2021 Apr.

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.

Keywords: epilepsy; exocytosis; intellectual disability; movement disorder; neurodegeneration; neurotoxin.

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References

REFERENCES

    1. Abeliovich, A., Schmitz, Y., Farinas, I., Abeliovich, A., Schmitz, Y., Fariñas, I., Choi-Lundberg, D., Ho, W. H., Castillo, P. E., Shinsky, N., Verdugo, J. M., Armanini, M., Ryan, A., Hynes, M., Phillips, H., Sulzer, D., & Rosenthal, A. (2000). Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron, 25, 239-252.
    1. Abramov, D., Guiberson, N. G. L., & Burre, J. (2020). STXBP1 encephalopathies: Clinical spectrum, disease mechanisms, and therapeutic strategies. Journal of Neurochemistry. https://doi.org/10.1111/jnc.15120
    1. Aguado, F., Majo, G., Ruiz-Montasell, B., Llorens, J., Marsal, J., & Blasi, J. (1999). Syntaxin 1A and 1B display distinct distribution patterns in the rat peripheral nervous system. Neuroscience, 88, 437-446. https://doi.org/10.1016/S0306-4522(98)00247-4
    1. Appel-Cresswell, S., Vilarino-Guell, C., Encarnacion, M., Sherman, H., Yu, I., Shah, B., Weir, D., Thompson, C., Szu-Tu, C., Trinh, J., Aasly, J. O., Rajput, A., Rajput, A. H., Jon Stoessl, A., & Farrer, M. J. (2013). Alpha-synuclein p. H50Q, a novel pathogenic mutation for Parkinson's disease. Movement Disorders, 28, 811-813. https://doi.org/10.1002/mds.25421
    1. Archer, B. T. 3rd, Ozcelik, T., Jahn, R., Francke, U., & Sudhof, T. C. (1990). Structures and chromosomal localizations of two human genes encoding synaptobrevins 1 and 2. Journal of Biological Chemistry, 265, 17267-17273.

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