Targeted expression of Hsap\SNCATP.Scer\UAS.cKa not only recapitulates Parkinson's disease motor symptoms but also the preceding non-motor symptoms such as an abnormal sleep-like behavior, altered locomotor activity and abnormal circadian periodicity.
Mutations in Hsap\SNCA (based on a structure-based design rationale) which increase neurotoxicity, show reduced fibril and β-structure formation and increased soluble oligomers in vitro.
Ectopic expression of Hsap\SNCATP.Scer\UAS.cKa under the control of either Scer\GAL4C164 or Scer\GAL4ple.PF results in defects in locomotion and a significant decrease in the distance crawled by third instar larvae per unit of time compared to controls.
Expression of Hsap\SNCATP.Scer\UAS.cKa in serotonergic and dopaminergic neurons, under the control of Scer\GAL4Ddc.PL, leads to a strong increase in both the number and length of sleep episodes respectively, when compared to controls in both light and dark phases. Expression of Hsap\SNCATP.Scer\UAS.cKa under the control of Scer\GAL4Ddc.PL leads to a significant reduction in the time the flies spend asleep during a 24 hour period.
Expression of Hsap\SNCATP.Scer\UAS.cKa in serotonergic and dopaminergic neurons, under the control of Scer\GAL4Ddc.PL alters circadian locomotor activity. Anticipation behaviour is maintained in young (1-3 days after eclosion) flies expressing Hsap\SNCATP.Scer\UAS.cKa. Old flies (30 days after eclosion) lose this behaviour. Hsap\SNCATP.Scer\UAS.cKa expression causes a phasing out of locomotion activity at the light-dark transition. This effect is further enhanced in older flies.
Young flies expressing Hsap\SNCATP.Scer\UAS.cKa under the control of Scer\GAL4Ddc.PL display wild-type circardian periodicity. Old flies shift their periodicity in a similar way to per mutants.
Expression of Hsap\SNCATP.Scer\UAS.cKa in DA neurons under the control of Scer\GAL4ple.PF causes a phase shift in circadian locomotor activity and gradually extends the circadian periodicity.
The expression of Hsap\SNCATP.Scer\UAS.cKa under the control of Scer\GAL4Ddc.PL results in significant decreases in adult lifespan, as compared to controls.
Hsap\SNCATP.UAS.cKa, Scer\GAL4C164 has abnormal locomotor behavior | third instar larval stage phenotype, suppressible by Rab8UASp.YFP, Scer\GAL4C164
Hsap\SNCATP.UAS.cKa, Scer\GAL4ple.PF has abnormal locomotor behavior | third instar larval stage phenotype, suppressible by Rab8UASp.YFP, Scer\GAL4ple.PF
The locomotion defects characteristic for third instar larvae expressing Hsap\SNCATP.Scer\UAS.cKa under the control of either Scer\GAL4C164 or Scer\GAL4ple.PF can be suppressed by co-expression of Rab8Scer\UAS.P\T.T:Avic\GFP-YFP : the decrease in the distance crawled by third instar larvae per unit of time is significantly ameliorated.