Drosophila as a model to study human brain degenerative diseases.
Drosophila has been an ideal system in which to identify molecules and define pathways involved in development, in part because of the powerful genetic approaches that are possible. Many of the molecules and pathways important in development in Drosophila are evolutionarily conserved between fly and human. With its highly evolved nervous system, amenability to genetic analysis, and the full genomic sequence available, Drosophila is a valuable tool for investigating and understanding the molecular mechanisms of neurodegenerative diseases.In order to have neurodegenerative Drosophila mutants, I screened EMS treated X chromosomes and P-element inserted 2nd and 3rd chromosomes in Drosophila for reduced life span and neurodegeneration. Twenty-one neurodegenerative mutants including bubblegum, spongecake, and eggroll were isolated and were named by virtue of their brain lesions. Each mutant has distinct pattern of degeneration in specific regions of the brain. Degeneration occurs in lamina and retina region in bubblegum. In spongecake vacuolization can only be seen in the optic lobe, especially in the medulla region. Multilamellated inclusions are wide-spread in the brain of eggroll. It showed not only do the pathologies iin fly brains resemble that of human diseases including Creutzfeldt Jakob disease, Tach-Sachs and Niemann-Pick disease, but the gene involved in the pathological pathway in the bubblegum mutant also functions as in the human adrenoleukodystrophy.
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Neurogenetics Branch (MSC1250), Building 10, Room 3B12, NINDS, NIH, MD 20892, Bethesda, USA