SWS/NTE-dependent neuropathy is the model system to study neurodegeneration

  • N. P. Matiytsiv


Today there is many described neurodegenerative D. melanogaster mutants, which characterized by development of degenerative changes in brain. One of them are a swiss cheese (sws) gene mutants. Mutations in this gene causes apoptosis of neurons and hyperwrapping of their somas by the glial cells, reducing of life expectancy and decrease of locomotion. The sws gene is the ortholog of mammal’s neuropathy target esterase (NTE / PNPLA6). NTE is s neuronal, transmembrane protein, that possesses serinesterase activity, and can be the target for neurotoxic organophosphorus compounds activity. Mutations in PNPLA6 gene cause number hereditary neurodegenerative disorders, which nowadays are incurable. The search for therapeutic agents require use of model objects because researches on humans have both methodical and ethical limitations. During two last decades D. melanogaster has proven itself as a good model for study of neurodegenerative diseases. In this review, we described general characteristics of D. melanogaster gene sws,
consequences of its mutations and provided evidences of high conservatism of gene product.

Keywords: gene swiss cheese, neuropathy target esterase, neurodegeneration, brain, life span.


Reiter L., Potocki L., Chien S., Gribskov M., Bier E. A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome Res. 2001. Vol. 11. P. 1114–1125. doi: 10.1101/gr.169101

Pandey U., Nichols C. Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery. Pharmacological Reviews. 2011. Vol. 63(2). P. 411–436. doi: 10.1124/pr.110.003293

Partridge L. Some highlights of research on aging with invertebrates. Aging Cell. 2009. Vol. 8. P. 509–513. doi: 10.1111/j.1474-9726.2009.00498.x

Mohylyak I., Chernyk Ya. Functioning of glia and neurodegeneration in Drosophila melanogaster. Cytology and Genetics. 2017. Vol. 51. P. 202–213. doi: 10.3103/S0095452717030094

Kretzschmar D., Hasan G., Sharma S., Heisenberg M., Benzer S. The swiss cheese mutant cause glial hyperwrapping and brain degeneration in Drosophila. J. Neurosci. 1997. Vol. 17. P. 7425–7432. doi: 10.1523/JNEUROSCI.17-19-07425.1997

Ryabova E., Matiytsiv N., Trush O., Mohylyak I., Kislik G., Melentev P., Sarantseva S. Swiss Cheese, Drosophila ortholog of hereditary spastic paraplegia gene NTE, maintains neuromuscular junction development and microtubule network; in Perveen F.K. (eds): Drosophila melanogaster – Model for Recent Advances in Genetics and Therapeutics, InTech, 2018. doi: 10.5772/intechopen.73077.

Matiytsiv N.P., Mohylyak I.I., Truhs O.I., Chernik Y.I. Motor activity of Drosophila melanogaster neurodegenerative mutants. Visnyk of the Odessa University. Series Biology. 2013. Vol. 18. P. 70–76. [in Ukranian] doi: 10.18524/2077-1746.2013.2(31).44771

Dutta S., Rieche F., Eckl N., Duch C., Kretzschmar D. Glial expression of Swiss cheese (SWS), the Drosophila orthologue of neuropathy target esterase (NTE), is required for neuronal ensheathment and function. Dis. Model Mech. 2016. Vol. 9. P. 283–294. doi: 10.1242/dmm.022236.

Mühlig-Versen M., da Cruz A.B., Tschäpe J. et al. Loss of Swiss cheese/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult Drosophila. J. Neurosci. 2005. Vol. 25. P. 2865–2873. doi: 10.1523/JNEUROSCI.5097-04.2005

da Cruz B., Wentzell J., Kretzschmar D. Swiss Cheese, a protein involved in progressive neurodegeneration, acts as a noncanonical regulatory subunit for PKA-C3. J. Neuroscience. 2008. Vol. 28. P. 10885–10892. doi: 10.1523/JNEUROSCI.3015-08.2008

Read D., Li Y., Chao M., Cavanagh J., Glynn P. Neuropathy Target Esterase Is Required for Adult Vertebrate Axon Maintenance. J. Neuroscience. 2009. Vol. 29, № 37. P. 11594–11600. doi.org/10.1523/jneurosci.3007-09.2009.

Sunderhaus E.R., Law A.D., Kretzschmar D. ER responses play a key role in Swiss-Cheese/Neuropathy Target Esterase-associated neurodegeneration. Neurobiol Dis. 2019. Vol. 130. P. 104520. doi: 10.1016/j.nbd.2019.104520.

Lush M.J., Li Y., Read D.J., Willis A.C., Glynn P. Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man. J. Biochem. 1998. Vol. 332. P. 1–4. doi: 10.1042/bj3320001

Glynn P. Neuropathy target esterase and phospholipid deacylation. Biochim Biophys Acta. 2005. Vol. 1736. P. 87–93. doi: 10.1016/j.bbalip.2005.08.002

Synofzik M., Gonzalez M. A., Lourenco C. M., Coutelier M. et al. PNPLA6 mutations cause Boucher-Neuhauser and Gordon Holmes syndromes as part of a broad neurodegenerative spectrum. J. of Neurology Brain. 2014. Vol. 137. P. 69–77. doi: 10.1093/brain/awt326.

Rainier S., Bui M., Mark E., Thomas D., Tokarz D. et al. Neuropathy target esterase gene mutations cause motor neurondisease. Am J Hum Genet. 2008. Vol. 82. P. 780–785. doi: 10.1016/j.ajhg.2007.12.018.