Neuropathy target esterase (NTE) is a molecular target for the organophosphorus compound-induced delayed neuropathy (OPIDN) and also one of the genetic factors responsible for the development of the hereditary spastic paraplegia (HSP), characterized by axon degeneration of motoneurons causing progressive lower-limb spastic paralysis. Both HSP and OPIDN are characterized by the distal axonopathy. The molecular mechanisms underlying the axonopathy involved in HSP and OPIDN are poorly understood. In order to have a beter understanding of the mechanisms that NTE is involved in, we used one of the homologs, human NTE. Swiss cheese (sws) is a Drosophila melanogaster ortholog of NTE with 39% homology. Mutations in sws as it was shown before lead to age-dependent neurodegeneration, structure alteration of glia cells, and reduced insect life span. To study SWS functions, we used the system of the third-instar larval neuromuscular junctions of D. melanogaster. In this study, we show that mutations in sws (sws 1 and sws 76−1) and SWS knockdown alter neuromuscular junction's morphology and synaptic microtubules organization.
Development and research of new neuroactive agents remain relevant because of neurodegenerative diseases incurability. We tested an experimental preparation created from the peptide blood components of Alzheimer's patients in remission period. It was assumed that this product contained autoneuroactive molecules that might have therapeutic or prophylactic potential. Experimental preparation was tested on Drosophila sws-dependent neurodegenerative model. One test system was presented by wild type Oregon R and sws 1 mutants; another one was presented by transgenic lines for UAS-GAL4 controlled knockdown of sws gene in glial cells. Adement and negative control BPAP (blood plasma components of Alzheimer's patients) were fed in two ways: for larvae or on adult stage. The effects of preparations were evaluated by the survival of tested flies. Flies with different genotypes, fed in different ways showed individual survival characteristics in each particular case. How ever, we did not detect any cases of survival increasing; conversely, in some cases Adement reduced survival. The results showed no influence or toxicity effect of Adement on both control individuals and flies with sws-dependent neurodegeneration.
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