ArticleNeuroscience bulletin2026
Agomelatine Targets Aquaporin-4 Polarization to Rescue Glymphatic Dysfunction in Parkinson's Disease.
Article in Neuroscience bulletin, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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Who cites it
7 citing papers in PubMed.
- The glymphatic-lymphatic axis: known pathways, open questions, and emerging roles in neurodegeneration.Translational neurodegeneration · 2026Review
- Convergent Astrocytic Failure in Parkinson's Disease: A System-Level Model of Pathogenesis and Treatment.Molecular neurobiology · 2026Review
- Sleep-circadian modulation of autophagy and glymphatic function: failure of coordinated brain clearance in Parkinson's disease.NPJ Parkinson's disease · 2026Review
- Alterations in the DTI-ALPS index and choroid plexus volume are associated with symptom severity in children with tic disorders.BMC neurology · 2026Article
- Aquaporin-4 Dysfunction in Depression: From Pathogenic Mechanisms to Novel Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Aquaporin-4 suppresses neuronal pyroptosis after ischemic stroke via the IκBα/NF-κB signaling pathway.Frontiers in immunology · 2026Article
- Recent Advances in Unraveling the Mechanisms of Pain and Itch: The Third Special Issue.Neuroscience bulletin · 2025Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Melatonin deficiency in Parkinson's disease (PD) patients correlates with impaired glymphatic function as measured by diffusion tensor imaging along the perivascular space (DTI-ALPS) index, suggesting circadian-regulated waste clearance as a therapeutic target. Unlike previous studies focusing on agomelatine's (AGM) antidepressant and sleep-regulating properties, we demonstrate its novel mechanism in PD treatment through glymphatic enhancement. Retrospective clinical analysis of PD patients revealed that AGM administration restored glymphatic function and improved motor performance. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced (MPTP) PD models, AGM alleviated glymphatic dysfunction and anxiety-like behaviors while reducing PD pathology. Crucially, AGM promoted aquaporin-4 (AQP4) polarization at astrocytic endfeet, as evidenced by RNA sequencing showing enhanced gap junction-related gene expression. The brain and muscle ARNT-like 1 (BMAL1)-mediated transcriptional regulation emerged as the key pathway underlying these effects. Our findings establish AGM as the first melatoninergic agent targeting the glymphatic-AQP4 axis in PD, shifting therapeutic strategies from symptomatic relief to disease modification. This provides clinical rationale for repurposing circadian regulators to decelerate PD progression through enhanced protein clearance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.