Reversible symptoms and clearance of mutant prion protein in an inducible model of a genetic prion disease in Drosophila melanogaster
| Autor: | R.A. Maue, A. Murali, Patrick J. Dolph |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Ataxia
Prions animal diseases Mutant Motor Activity lcsh:RC321-571 Reversibility Mutant protein medicine Animals Gerstmann-Straussler-Scheinker Disease Missense mutation Cholinergic neuron lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Inducible model of GSS Clearance of misfolded prion protein Genetics Models Genetic biology Neurodegeneration medicine.disease biology.organism_classification P101L nervous system diseases Disease Models Animal Drosophila melanogaster Neurology Mutation Kuru medicine.symptom |
| Zdroj: | Neurobiology of Disease, Vol 67, Iss, Pp 71-78 (2014) |
| ISSN: | 0969-9961 |
| Popis: | Prion diseases are progressive disorders that affect the central nervous system leading to memory loss, personality changes, ataxia and neurodegeneration. In humans, these disorders include Creutzfeldt–Jakob disease, kuru and Gerstmann–Straussler–Scheinker (GSS) syndrome, the latter being a dominantly inherited prion disease associated with missense mutations in the gene that codes for the prion protein. The exact mechanism by which mutant prion proteins affect the central nervous system and cause neurological disease is not well understood. We have generated an inducible model of GSS disease in Drosophila melanogaster by temporally expressing a misfolded form of the murine prion protein in cholinergic neurons. Flies accumulating this mutant protein develop motor abnormalities which are associated with electrophysiological defects in cholinergic neurons. We find that, upon blocking the expression of the mutant protein, both behavioral and electrophysiological defects can be reversed. This represents the first case of reversibility reported in a model of genetic prion disease. Additionally, we observe that endogenous mechanisms exist within Drosophila that are capable of clearing the accumulated prion protein. |
| Databáze: | OpenAIRE |
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