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DIMETHYL FUMARATE REPURPOSING AGAINST ALPHA-SYNUCLEIN-INDUCED TOXICITY IN MICE
Michela Salvadèand 14 co-authors
University of Milan
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS01-07AM-469
Presentation
Date TBA
Board: PS01-07AM-469
Event Information
Poster Board
PS01-07AM-469
Poster
View posterAbstract
Drug repurposing strategies have increased the possibility of proposing new therapeutic approaches in neurodegenerative diseases. To facilitate translation from animals to humans, employing state-of-the-art preclinical models is essential. We used alpha-synuclein-based models to gain insights into alpha-synucleinopathies, particularly Parkinson’s disease.
Here, we aimed to repurpose dimethyl fumarate (DMF), an anti-inflammatory molecule used for the therapy of multiple sclerosis, to counteract alpha-synuclein-induced detrimental effects. We bilaterally injected mice into the dorsal striatum with alpha-synuclein preformed fibrils (alpha-syn-PFF) to recapitulate early phases of the disease. We set the endpoint at 12 weeks after injections of alpha-syn-PFF or PBS, as control. A group of alpha-syn-PFF-injected mice was chronically orally treated with DMF during the last four weeks prior to sacrifice.
First, we demonstrated that DMF treatment reversed most of alpha-synuclein-induced behavioural deficits. Moreover, electrophysiological analyses revealed that DMF treatment fully rescued alpha-synuclein-induced detrimental effects on synaptic plasticity of medium spiny neurons. Additionally, DMF treatment reduced the presence of toxic phosphorylated alpha-synuclein inclusions in the dorsal striatum of mice.
Through biochemical, molecular, and immunohistochemical approaches, we dissected DMF’s mechanisms of action. We demonstrated that DMF beneficial effects were associated with the upregulation of the master regulator Nrf2 and by the functional rescue of alpha-synuclein-induced deficits in S100beta-positive astroglial cells in the mouse striatum.
Overall, this study further supports the translational potential of DMF as a disease-modifying treatment for alpha-synucleinopathies.
Here, we aimed to repurpose dimethyl fumarate (DMF), an anti-inflammatory molecule used for the therapy of multiple sclerosis, to counteract alpha-synuclein-induced detrimental effects. We bilaterally injected mice into the dorsal striatum with alpha-synuclein preformed fibrils (alpha-syn-PFF) to recapitulate early phases of the disease. We set the endpoint at 12 weeks after injections of alpha-syn-PFF or PBS, as control. A group of alpha-syn-PFF-injected mice was chronically orally treated with DMF during the last four weeks prior to sacrifice.
First, we demonstrated that DMF treatment reversed most of alpha-synuclein-induced behavioural deficits. Moreover, electrophysiological analyses revealed that DMF treatment fully rescued alpha-synuclein-induced detrimental effects on synaptic plasticity of medium spiny neurons. Additionally, DMF treatment reduced the presence of toxic phosphorylated alpha-synuclein inclusions in the dorsal striatum of mice.
Through biochemical, molecular, and immunohistochemical approaches, we dissected DMF’s mechanisms of action. We demonstrated that DMF beneficial effects were associated with the upregulation of the master regulator Nrf2 and by the functional rescue of alpha-synuclein-induced deficits in S100beta-positive astroglial cells in the mouse striatum.
Overall, this study further supports the translational potential of DMF as a disease-modifying treatment for alpha-synucleinopathies.
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