| First Author | Morawska MM | Year | 2021 |
| Journal | Sci Transl Med | Volume | 13 |
| Issue | 623 | Pages | eabe7099 |
| PubMed ID | 34878820 | Mgi Jnum | J:344060 |
| Mgi Id | MGI:7279052 | Doi | 10.1126/scitranslmed.abe7099 |
| Citation | Morawska MM, et al. (2021) Slow-wave sleep affects synucleinopathy and regulates proteostatic processes in mouse models of Parkinson's disease. Sci Transl Med 13(623):eabe7099 |
| abstractText | Slow-wave sleep (SWS) modulation in rodent models of Alzheimer's disease alters extracellular amyloid burden. In Parkinson's disease (PD), SWS appears to be closely linked with disease symptoms and progression. PD is characterized by damaging intracellular alpha-synuclein (alphaSyn) deposition that propagates extracellularly, contributing to disease spread. Intracellular alphaSyn is sensitive to degradation, whereas extracellular alphaSyn may be eliminated by glymphatic clearance, a process increased during SWS. Here, we explored whether long-term slow-wave modulation in murine models of PD presenting alphaSyn aggregation alters pathological protein burden and, thus, might constitute a valuable therapeutic target. Sleep-modulating treatments showed that enhancing slow waves in both VMAT2-deficient and A53T mouse models of PD reduced pathological alphaSyn accumulation compared to control animals. Nonpharmacological sleep deprivation had the opposite effect in VMAT2-deficient mice, severely increasing the pathological burden. We also found that SWS enhancement was associated with increased recruitment of aquaporin-4 to perivascular sites, suggesting a possible increase of glymphatic function. Furthermore, mass spectrometry data revealed differential and specific up-regulation of functional protein clusters linked to proteostasis upon slow wave-enhancing interventions. Overall, the beneficial effect of SWS enhancement on neuropathological outcome in murine synucleinopathy models mirrors findings in models of Alzheimer. Modulating SWS might constitute an effective strategy for modulating PD pathology in patients. |
