Pharmacological interventions targeting α-synuclein aggregation triggered REM sleep behavior disorder and early development of Parkinson's disease

Lida Du, Xiaoli He, Xiaonuo Fan, Xiaoya Wei, Linhao Xu, Tuo Liang, Chunbo Wang, Ya Ke, Wing-ho Yung*

*Corresponding author for this work

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

6 Citations (Scopus)

Abstract

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by elevated motor behaviors and dream enactments in REM sleep, often preceding the diagnosis of Parkinson's disease (PD). As RBD could serve as a biomarker for early PD developments, pharmacological interventions targeting α-synuclein aggregation triggered RBD could be applied toward early PD progression. However, robust therapeutic guidelines toward PD-induced RBD are lacking, owing in part to a historical paucity of effective treatments and trials. We reviewed the bidirectional links between α-synuclein neurodegeneration, progressive sleep disorders, and RBD. We highlighted the correlation between RBD development, α-synuclein aggregation, and neuronal apoptosis in key brainstem regions involved in REM sleep atonia maintenance. The current pharmacological intervention strategies targeting RBD and their effects on progressive PD are discussed, as well as current treatments for progressive neurodegeneration and their effects on RBD. We also evaluated emerging and potential pharmacological solutions to sleep disorders and developing synucleinopathies. This review provides insights into the mechanisms and therapeutic targets underlying RBD and PD, and explores bidirectional treatment effects for both diseases, underscoring the need for further research in this area. © 2023 Elsevier Inc. All rights reserved.
Original languageEnglish
Article number108498
JournalPharmacology & Therapeutics
Volume249
Online published25 Jul 2023
DOIs
Publication statusPublished - Sept 2023

Research Keywords

  • Parkinson's disease
  • Pharmacological interventions
  • REM sleep behavior disorder
  • α-Synuclein neurodegeneration

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