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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.

Inhibition of Ref(2)P, the Drosophila homologue of the p62/SQSTM1 gene, increases lifespan and leads to a decline in motor function