PTPRD as a candidate druggable target for therapies for restless legs syndrome?

Abstract

The gene that encodes the protein tyrosine phosphatase D (PTPRD) may be related to brain circuits associated with sleep, and has been seen as an interesting molecule, a “druggable” drug target. This gene is a potential candidate for increasing therapeutic advances in restless legs syndrome, a sleep‐related movement disorder, that manifests as an uncontrollable desire to move limbs (legs) to relieve uncomfortable sensations. Changes in the PTPRD gene expression may increase the chance of developing this syndrome. Treatment with pramipexole is used in restless legs syndrome. This study aims to verify the effect of treatment with pramipexole on the PTPRD expression, as well as on the sleep pattern in an animal model for restless legs syndrome. For this, an animal model of sleep‐related movement disorders (spontaneously hypertensive rats) was distributed in groups: (a) spontaneously hypertensive rats−control; (b) spontaneously hypertensive rats−pramipexole (0.125 mg kg−1 for 4 weeks). The analyses of PTPRD gene and protein expression were performed in the striatum and spinal cord by quantitative real‐time polymerase chain reaction and indirect enzyme‐linked immunosorbent assay, respectively. Electrocorticographic and electromyographic analyses were performed. There was no difference in the PTPRD mRNA levels, as well as in the protein levels, although a tendency has been observed for decreased gene expression in the striatum and increased protein expression in the spinal cord in the spontaneously hypertensive rats−pramipexole group. Pramipexole improved the animals' sleep pattern. Thus, the treatment with pramipexole in the evaluated dose and time tended to alter the expression of the PTPRD protein in the spinal cord, in addition to significantly improving the sleep pattern.

Association between sleep disorders and physical activity in middle-aged Americans: Data from NHANES 2007-2018

“…The second exercise increased PTPRD (protein tyrosine phosphatase receptor delta-type) protein levels, decreased tyrosine hydroxylase (TH) protein levels and improved sleep parameters in both cycles of restless leg syndrome. The results of this study showed an improvement in sleep parameters in both cycles of restless leg syndrome (Wang et al, 2022) (Morais et al, 2023). However, one study showed that excessively strenuous physical activity disrupts redox homeostasis against oxidative stress (Kruk et al, 2019), which disrupts the antioxidant status of the body and thus affects sleep quality.…”

“…For instance, physical activity has been proven to be bene cial for MCI and dementia (Nuzum et al, 2020). In addition, functional recovery in patients with bidirectional depression (Hamada et al, 2023), neuroendocrine abnormalities in Parkinson's disease (Luthra et al, 2023), restless leg syndrome(RLS) (Morais et al, 2023), have all demonstrated improvement. However, research on exercise and sleep disorders in middle-aged adults is still lacking.…”

Exploration of restless legs syndrome under the new concept: A review

“…Studies of the effects of iron deficiency on the spinal dopamine system and brain have suggested that adenosine may play an important role in the disease. Clinical and animal studies have demonstrated a putative link between RLS risk alleles and iron [ 69 ] and basal ganglia development. [ 29 ] Despite the remarkable convergence phenomena,…”

Protein tyrosine phosphatase receptor type delta (PTPRD) gene in an animal model of restless legs syndrome

“…Some research has explored the PTPRD in RLS animals models (Drgonova et al, 2015; Morais et al, 2020; Uhl & Martinez, 2019; Yin et al, 2012); however, still it has not been demonstrated the sequencing of the PTPRD gene in the SHR and WK strains. Morais et al (2020) observed that the use of pramipexole in SHRs may alter PTPRD protein content in the spinal cord; however, that study did not analyse the baseline levels of PTPRD compared to another strain that does not develop RLS.…”