title: Mitochondria-Targeting Ceria Nanoparticles as Antioxidants for Alzheimer's Disease.
abstract: Mitochondrial oxidative stress is a key pathologic factor in neurodegenerative diseases, including Alzheimer's disease. Abnormal generation of reactive oxygen species (ROS), resulting from mitochondrial dysfunction, can lead to neuronal cell death. Ceria (CeO2) nanoparticles are known to function as strong and recyclable ROS scavengers by shuttling between Ce(3+) and Ce(4+) oxidation states. Consequently, targeting ceria nanoparticles selectively to mitochondria might be a promising therapeutic approach for neurodegenerative diseases. Here, we report the design and synthesis of triphenylphosphonium-conjugated ceria nanoparticles that localize to mitochondria and suppress neuronal death in a 5XFAD transgenic Alzheimer's disease mouse model. The triphenylphosphonium-conjugated ceria nanoparticles mitigate reactive gliosis and morphological mitochondria damage observed in these mice. Altogether, our data indicate that the triphenylphosphonium-conjugated ceria nanoparticles are a potential therapeutic candidate for mitochondrial oxidative stress in Alzheimer's disease.
authors: Center for Nanoparticle Research, Institute for Basic Science (IBS) , Seoul 151-742, Republic of Korea.|School of Chemical and Biological Engineering and Institute of Chemical Processes, Seoul National University , Seoul 151-742, Republic of Korea.
authors: Hyek Jin
authors: HJ
authors: Kwon
authors: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine , Seoul 110-799, Republic of Korea.
authors: Moon-Yong
authors: MY
authors: Cha
authors: Center for Nanoparticle Research, Institute for Basic Science (IBS) , Seoul 151-742, Republic of Korea.
authors: Dokyoon
authors: D
authors: Kim
authors: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine , Seoul 110-799, Republic of Korea.
authors: Dong Kyu
authors: DK
authors: Kim
authors: Center for Nanoparticle Research, Institute for Basic Science (IBS) , Seoul 151-742, Republic of Korea.|School of Chemical and Biological Engineering and Institute of Chemical Processes, Seoul National University , Seoul 151-742, Republic of Korea.
authors: Min
authors: M
authors: Soh
authors: Center for Nanoparticle Research, Institute for Basic Science (IBS) , Seoul 151-742, Republic of Korea.|School of Chemical and Biological Engineering and Institute of Chemical Processes, Seoul National University , Seoul 151-742, Republic of Korea.
authors: Kwangsoo
authors: K
authors: Shin
authors: Center for Nanoparticle Research, Institute for Basic Science (IBS) , Seoul 151-742, Republic of Korea.|School of Chemical and Biological Engineering and Institute of Chemical Processes, Seoul National University , Seoul 151-742, Republic of Korea.
authors: Taeghwan
authors: T
authors: Hyeon
authors: Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine , Seoul 110-799, Republic of Korea.
authors: Inhee
authors: I
authors: Mook-Jung
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D002563:Cerium / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D006367:HeLa Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000737:chemistry; D018384:Oxidative Stress
chemical_list: D000975:Antioxidants; D009943:Organophosphorus Compounds; D002563:Cerium; C030583:ceric oxide
keywords: Alzheimer’s disease; ceria nanoparticles; mitochondria; reactive oxygen species; therapeutic agents