U-133, a Chaperone Inducer, Eliminates Sleep Disturbances in a Model of the Preclinical Stage of Parkinson’s Disease in Aged Rats

Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disease that is closely associated with aging. It is considered incurable due to its late diagnosis and the use of symptomatic treatment, which cannot alter the molecular mechanisms of sleep disruption nor the neurodegenerative processes that develop with aging and PD progression. The present study assesses the therapeutic potential of a novel chaperone inducer, U-133 (acetyl 2,3,7-tris- O -glucoside echinochrome), in the preclinical stage of PD modelled in aged rats via inhibition of the proteasomal system in the brain. U-133 is a derivative of the sea-urchin pigment echinochrome (2,3,5,7,8-pentahydroxy-1,4-naphthoquinone). It is produced by glycosylation, which possesses neuroprotective, antioxidant, and anticancer properties. The administration of U-133, which induces the synthesis of Hsp 70i and HSP 40 heat-shock proteins in the brain, precludes an increase in the light-sleep (drowsiness) stage and a decrease in the total time of deep, slow-wave sleep, both of which occur with the progression of the preclinical stage of PD modelled in aged Wistar rats. Deep, slow-wave sleep is thought to promote glymphatic clearance and to accelerate protein synthesis. Thus, the U-133-induced increase in the proportion of deep, slow-wave sleep as compared to the preclinical model is considered to have a neuroprotective effect that contributes to the intensification of the restorative function of neurons and counteracts the progression of neurodegeneration.