Distinctive Effects of Fullerene C60 and Fullerenol C60(OH)24 Nanoparticles on Histological, Molecular and Behavioral Hallmarks of Alzheimer’s Disease in APPswe/PS1E9 Mice
Askarova S. Sitdikova K. Kassenova A. Chaprov K. Svirin E. Tsoy A. de Munter J. Gorlova A. Litavrin A. Deikin A. Nedorubov A. Appazov N. Kalueff A. Chernopiatko A. Strekalova T.
July 2025Multidisciplinary Digital Publishing Institute (MDPI)
Antioxidants
2025#14Issue 7
Fullerenes and fullerenols exhibit antioxidant and anti-inflammatory properties, making them promising candidates for Alzheimer’s disease (AD) therapy. Unlike conventional anti-inflammatory drugs, these compounds have multitargeted effects, including their ability to inhibit amyloid fibril formation. However, few studies have explored their efficacy in high-validity AD models. Female APPswe/PS1E9 (APP/PS1) mice and their wild-type (WT) littermates were orally administered with fullerene C60 (0.1 mg/kg/day) or fullerenol C60(OH)24 (0.15 mg/kg/day) for 10 months starting at 2 months of age. Behavioral assessments were performed at 12 months of age. Amyloid plaque density and size were analyzed in the brain regions using Congo red staining. The expression of genes related to inflammation and plasticity was examined, and an in vitro assay was used to test the toxicity of fullerenol and its effect on amyloid β peptide 42 (Aβ42)-induced reactive oxygen species (ROS) production. Fullerenol reduced the maximum plaque size in the cortex and hippocampus, decreased the small plaque density in the hippocampus and thalamus, and prevented an increase in glial fibrillary acidic protein (GFAP) positive cell density in the mutants. Both treatments improved cognitive and emotional behaviors and reduced Il1β and increased Sirt1 expression. In vitro, fullerenol was non-toxic across a range of concentrations and reduced Aβ42-induced ROS production in brain endothelial cells and astrocytes. Long-term administration of fullerene or fullerenol improved behavioral and molecular markers of AD in APP/PS1 mice, with fullerenol showing additional benefits in reducing amyloid burden.
Alzheimer’s disease , antioxidants , APPswe/PS1E9 mice , fullerene C60 , fullerenol C60(OH)24
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Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Astana, 010000, Kazakhstan
Institute of General Pathology and Pathophysiology, Moscow, 125315, Russian Federation
Department of General Biology and Genomics, Faculty of Natural Sciences, L.N. Gumilyov Eurasian National University, Astana, 010000, Kazakhstan
Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Chernogolovka, 119071, Russian Federation
Neuroplast BV, Maastricht, 6222 NK, Netherlands
Research and Education Resource Center, Peoples Friendship University of Russia, Moscow, 117198, Russian Federation
Department of Normal Physiology, Sechenov First Moscow State Medical University, Moscow, 119991, Russian Federation
Laboratory of Genetic Technology and Gene Editing for Biomedicine and Veterinary, National Research, Belgorod State University, Belgorod, 308015, Russian Federation
Laboratory of Engineering Profile Physical and Chemical Methods of Analysis, Korkyt Ata Kyzylorda University, Kyzylorda, 120014, Kazakhstan
Department of Biosciences and Bioinformatics, Suzhou Municipal Key Laboratory of Neurobiology and Cell Signaling, School of Science, Xi’an Jiaotong-Liverpool University, Suzhou, 215123, China
Center for Life Sciences
Institute of General Pathology and Pathophysiology
Department of General Biology and Genomics
Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry
Neuroplast BV
Research and Education Resource Center
Department of Normal Physiology
Laboratory of Genetic Technology and Gene Editing for Biomedicine and Veterinary
Laboratory of Engineering Profile Physical and Chemical Methods of Analysis
Department of Biosciences and Bioinformatics
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