Emily P Hurley1, Brian E Staveley2. 1. Department of Biology, Memorial University of Newfoundland, St. Johns', NL, A1B 3X9, Canada. 2. Department of Biology, Memorial University of Newfoundland, St. Johns', NL, A1B 3X9, Canada. bestave@mun.ca.
Abstract
OBJECTIVE: Sequestosome 1 (p62/SQSTM1) is a multifunctional scaffold/adaptor protein encoded by the p62/SQSTM1 gene with function in cellular homeostasis. Mutations in the p62/SQSTM1 gene have been known to be associated with patients with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson disease (PD). The aim of the present study was to create a novel model of human neurogenerative disease in Drosophila melanogaster by altering the expression of Ref(2)P, the Drosophila orthologue of the human p62/SQSTM1 gene. Ref(2)P expression was altered in all neurons, the dopaminergic neurons and in the motor neurons, with longevity and locomotor function assessed over time. RESULTS: Inhibition of Ref(2)P resulted in a significantly increased median lifespan in the motor neurons, followed by a severe decline in motor skills. Inhibition of Ref(2)P in the dopaminergic neurons resulted in a significant, but minimal increase in median lifespan, accompanied by a drastic decline in locomotor function. Inhibition of Ref(2)P in the ddc-Gal4-expressing neurons resulted in a significant increase in median lifespan, while dramatically reducing motor function.
OBJECTIVE: Sequestosome 1 (p62/SQSTM1) is a multifunctional scaffold/adaptor protein encoded by the p62/SQSTM1 gene with function in cellular homeostasis. Mutations in the p62/SQSTM1 gene have been known to be associated with patients with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson disease (PD). The aim of the present study was to create a novel model of human neurogenerative disease in Drosophila melanogaster by altering the expression of Ref(2)P, the Drosophila orthologue of the human p62/SQSTM1 gene. Ref(2)P expression was altered in all neurons, the dopaminergic neurons and in the motor neurons, with longevity and locomotor function assessed over time. RESULTS: Inhibition of Ref(2)P resulted in a significantly increased median lifespan in the motor neurons, followed by a severe decline in motor skills. Inhibition of Ref(2)P in the dopaminergic neurons resulted in a significant, but minimal increase in median lifespan, accompanied by a drastic decline in locomotor function. Inhibition of Ref(2)P in the ddc-Gal4-expressing neurons resulted in a significant increase in median lifespan, while dramatically reducing motor function.
Authors: Bryan J Bartlett; Pauline Isakson; Jan Lewerenz; Heriberto Sanchez; Roxanne W Kotzebue; Robert C Cumming; Greg L Harris; Ioannis P Nezis; David R Schubert; Anne Simonsen; Kim D Finley Journal: Autophagy Date: 2011-06-01 Impact factor: 16.016
Authors: Wei Jing Liu; Lin Ye; Wei Fang Huang; Lin Jie Guo; Zi Gan Xu; Hong Luan Wu; Chen Yang; Hua Feng Liu Journal: Cell Mol Biol Lett Date: 2016-12-13 Impact factor: 5.787