Expanded Polyglutamine Protein Forms Nuclear Inclusions and Causes Neural Degeneration in Drosophila
Year: 1998
Type: article
Abstract: Spinocerebellar ataxia type 3 (SCA3/MJD) is one of at least eight human neurodegenerative diseases caused by glutamine-repeat expansion. We have recreated glutamine-repeat disease in Drosophila using a segment of the SCA3/MJD protein. Targeted expression of the protein with an expanded polyglutamine repeat led to nuclear inclusion (NI) formation and late-onset cell degeneration. Differential sensitivity to the mutant transgene was observed among different cell types, with neurons being particularly susceptible; NI formation alone was not sufficient for degeneration. The viral antiapoptotic gene P35 mitigated polyglutamine-induced degeneration in vivo. Our results demonstrate that cellular mechanisms of human glutamine-repeat disease are conserved in invertebrates. This fly model will aid in identifying additional factors that modulate neurodegeneration.
Source: Cell
Authors: John M Warrick, Henry L Paulson, Gladys L Gray-Board, Quang T Bui, Kenneth H Fischbeck, Randall N Pittman, Nancy M Bonini
Institutions: University of Pennsylvania, University of Iowa
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $11,400
Funder: American Academy of Neurology
OpenAlex ID: W2135124405