Lazopulo, S. | bioRxiv Science

bioRxiv2024

Regulation of proteostasis by sleep through autophagy in Drosophila models of Alzheimer's Disease

Sleep and circadian rhythm dysfunctions are common clinical features of Alzheimers Disease (AD). Increasing evidence suggests that in addition to being a symptom, sleep disturbances can also drive the progression of neurodegeneration. Protein aggregation is a pathological hallmark of AD, however the molecular pathways behind how sleep affects protein homeostasis remain elusive. Here we demonstrate that sleep modulation influences proteostasis and the progression of neurodegeneration in Drosophila models of Tauopathy. We show that sleep deprivation enhanced Tau aggregational toxicity resulting in exacerbated synaptic degeneration. In contrast, sleep induction using gaboxadol led to reduced hyperphosphorylated Tau accumulation in neurons as a result of modulated autophagic flux and enhanced clearance of ubiquitinated Tau, suggesting altered protein processing and clearance that resulted in improved synaptic integrity and function. These findings highlight the complex relationship between sleep and autophagy, in regulating protein homeostasis, and the neuroprotective potential of sleep-enhancing therapeutics to slow the progression or delay the onset of neurodegeneration.

neuroscience↗

bioRxiv2019

Daytime Color Preference in Drosophila Depends on the Circadian Clock and TRP Channels

By guiding animals towards food and shelter and repelling them from potentially harmful situations, light discrimination according to colour can confer survival advantages1,2. Such colour-dependent behaviour may be experiential or innate. Data on innate colour preference remain controversial in mammals3 and limited in simpler organisms4-7. Here we show that when given a choice among blue, green and dim light, fruit flies exhibit an unexpectedly complex pattern of colour preference that changes with the time of day. Flies show a strong preference for green in the early morning and late afternoon, a reduced green preference at midday and a robust avoidance of blue throughout the day. Genetic manipulations reveal that the peaks in green preference require rhodopsin-based photoreceptors, and are controlled by the circadian clock. The midday reduction in green preference in favour of dim light depends on the Transient Receptor Potential (TRP) channels dTRPA1 and Pyrexia (Pyx), and is also timed by the clock. In contrast, blue avoidance is primarily mediated by class IV multidendritic neurons, requires the TRP channel Painless (Pain) and is independent of the clock. With unexpected roles for several TRP channels in Drosophila colour-specific phototransduction, our results reveal distinct pathways of innate colour preference that coordinate the flys behavioural dynamics in ambient light.

neuroscience↗