ArticleMovement disorders : official journal of the Movement Disorder Society2026
Perampanel Blocks Transsynaptic α-Synuclein Propagation and Neurodegeneration in a Mouse Model of Lewy Body Disease.
Article in Movement disorders : official journal of the Movement Disorder Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
backgroundTranssynaptic α-synuclein propagation plays a crucial role in the progression of Lewy body disease. We previously demonstrated that an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, perampanel, blocks neuronal uptake of α-synuclein preformed fibrils (PFFs) in an activity-dependent manner.
objectivesWe aimed to elucidate the underlying mechanisms of this effect and whether perampanel inhibits transsynaptic α-synuclein propagation.
methodsNeuronal uptake of PFFs was evaluated in mouse primary hippocampal neurons using PFFs labeled with pH-sensitive dye. The levels of dynamin1 and phosphorylated dynamin1 were analyzed in wild-type mice treated with perampanel using western blotting. The time course of clearance of PFFs injected into the olfactory bulb was examined in Snca knockout mice. α-Synuclein pathology and neurodegeneration were evaluated in PFF-injected A53T BAC-SNCA transgenic mice with perampanel or vehicle treatment for 2 and 9 months after the removal of injected PFFs.
resultsNeuronal uptake of PFFs was blocked by a dynamin inhibitor but not by a clathrin inhibitor in vitro. Oral administration of perampanel significantly increased the level of phosphorylated dynamin1 in mouse brains, suggesting that perampanel suppresses dynamin-dependent endocytosis in vivo. PFFs injected into the olfactory bulb disappeared within 1 week. In A53T BAC-SNCA transgenic mice injected with PFFs, perampanel treatment starting 1 week after PFFs injection reduced the amount of α-synuclein pathology in second- or higher-order regions, but not in first-order regions, from the injection site and ameliorated neurodegeneration.
conclusionsPerampanel could be a disease-modifying drug for Lewy body disease that modulates transsynaptic α-synuclein propagation, presumably by suppressing dynamin-dependent endocytosis. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.