Latest Study reveals that an important signalling pathway which helps in protecting brain cells from several neurodegenerative diseases including Parkinson’s disease is also required for sleep in zebrafish and fruit flies.
The findings of the recent study support the link between neurodegenerative disorders and sleep loss. This mechanism is observed in two distantly related species so it is likely to exist in humans too. It can support new strategies for treating neurodegenerative diseases as well as sleeping disorders.
The findings of the study “Evolutionarily Conserved Regulation of Sleep by the Protein Translational Regulator PERK” are published in Current Biology.
Sleeping disorders are one of the common features of neurodegenerative diseases. Although the link between neurodegenerative disorders and sleep is still unclear, there is evidence found in mice that during sleeping their brain ramps up the proteostasis, the process of clearing of harmful protein clumps that clutter the brain.
Clumps of alpha-synuclein protein in brain cells are the symbol of Parkinson’s disease.
Researchers said that sleep could be responsible for regulating the proteostasis in the brain which explains the link between sleep and neurological health.
Cellular proteostasis is the coordination of production and distribution of protein, and when it is disrupted by proteins clumping, the process called unfolded protein response (UPR) becomes activated. It slows down the protein production in this way allows the clearance of clumps and restores the mechanism of proteostasis and prevent cell death.
However, the link between sleep and UPR remains unclear.
The team of researchers at the University of Pennsylvania with the help of investigators at the California Institute of Technology examined the role of the pathway that is controlled by an enzyme known as PKR-like Kinase (PKRK) which mediates the activation of UPR.
Researchers at the University of Pennsylvania, in collaboration with investigators at the California Institute of Technology, studied the role of a pathway which is controlled by the enzyme PKR-like ER kinase (PERK) which is responsible for mediating UPR activation.
As the UPR mechanism is common in many species, the researchers used zebrafish as an example of vertebrates and fruit flies to represent invertebrate species.
Sleep deprivation leads to the activation of the PERK pathway in several species. Researchers were focused to understand if the activation of the PERK pathway was specific to sleep deprivation or if it could appear over the period of normal wakefulness.
Researchers tested the marker for the activation of this pathway in fruit flies at the start of the day and at the end of the day. This specific marker was observed to be elevated at the end of the day, showing that activation of the PERK pathway was linked to wakefulness.
They used a genetic approach for lowering the PERK production in neurons of fruit flies, they significantly slept less during both the night and day time and that decreases in the sleep length and number of sleeping bouts.
On the other hand, the overproduction of PERK y almost 14-fold led to an increase in sleep during both the night and day time due to the increase in the sleeping bouts and length.
These findings demonstrated that pathways related to protein synthesis like PERK could provide better insight into the relationship between proteostasis and sleep. The study findings suggest that sleep may be responsible for mitigating cellular stress which is caused by wakefulness.