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- Title
Molecular mechanisms of melatonin-induced alleviation of synaptic dysfunction and neuroinflammation in Parkinson’s disease: a review.
- Authors
GUO, Y.-L.; WEI, X.-J.; ZHANG, T.; SUN, T.
- Abstract
This review focuses on melatonin’s role in advancing Parkinson’s disease (PD) pathogenesis by inhibiting synaptic dysfunction and neuroinflammation. The early pathological changes in PD, caused by SNCA/ PARK1 and LRRK2/PARK8-mediated synaptic vesicle endocytosis during the early pathogenesis of PD, are briefly reviewed. The pathological changes related to synaptic plasticity and dendrites caused by synaptic dysfunction in neurotoxin 6-hydroxydopamine (6-OHDA) and 1-methl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)-induced PD models are also discussed. The molecular mechanisms of pathological changes in PD, caused by the activation of microglia, astrocytes, and inflammatory vesicles, are discussed. The effectiveness of melatonin (MLT) in the restoration of dopaminergic neurons in the substantia nigra (SNc) has been established. MLT can upregulate dendritic numbers and restore synaptic plasticity by inhibiting alpha-synuclein aggregation and neurotoxicity. These functions of MLT improve sleep patterns in PD patients and suppresses synaptic dysfunction by inhibiting the overactivation of the PKA/CREB/ BDNF signaling pathway and reactive oxygen species (ROS) production. MLT can maintain the typical transport and release of neurotransmitters. MLT also reduces neuroinflammation by promoting microglia 2 (M2) polarization, which reduces the expression of inflammatory cytokines. Additionally, MLT stimulates the activation of the retinoic acid receptor-related orphan receptor α (RORα) ligand and inhibits the activation of the Recombinant Sirtuin 1 (SIRT1)-dependent pathway, the NLR family pyridine structure domain 3 (NLRP3) inflammasome. By integrating the latest advances in synaptic dysfunction and neuroinflammation-related PD, researchers can develop clinical interventions for treating PD and further explore the pathological hallmarks of prodromal PD.
- Subjects
PARKINSON'S disease; PATHOLOGICAL physiology; NEUROINFLAMMATION; RETINOIC acid receptors; FAMILY structure; NEUROPLASTICITY; DENDRITES; DOPAMINERGIC neurons
- Publication
European Review for Medical & Pharmacological Sciences, 2023, Vol 27, Issue 11, p5070
- ISSN
1128-3602
- Publication type
Article