title: Nec-1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 mice.
abstract: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive symptoms of learning and memory deficits. Such cognitive impairments are attributed to brain atrophy resulting from progressive neuronal and synaptic loss; therefore, alleviation of neural cell death is as an important target of treatment as other classical hallmarks of AD, such as aggregation of amyloid-β (Aβ) and hyperphosphorylation of tau. Here, we found that an anti-necroptotic molecule necrostatin-1 (Nec-1) directly targets Aβ and tau proteins, alleviates brain cell death and ameliorates cognitive impairment in AD models. In the cortex and hippocampus of APP/PS1 double-transgenic mice, Nec-1 treatment reduced the levels of Aβ oligomers, plaques and hyperphosphorylated tau without affecting production of Aβ, while it altered the levels of apoptotic marker proteins. Our results showing multiple beneficial modes of action of Nec-1 against AD provide evidence that Nec-1 may serve an important role in the development of preventive approach for AD.
authors.affiliation: Convergence Research Center for Dementia and Center for Neuro-Medicine, Brain Science Institute Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Seung-Hoon
authors.identifier: 0000-0002-6880-8861
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Convergence Research Center for Dementia and Center for Neuro-Medicine, Brain Science Institute Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Dongkeun Kenneth
authors.initials: DK
authors.lastname: Lee
authors.affiliation: Convergence Research Center for Dementia and Center for Neuro-Medicine, Brain Science Institute Korea Institute of Science and Technology, Seoul, Korea.
authors.forename: Jisu
authors.initials: J
authors.lastname: Shin
authors.affiliation: Convergence Research Center for Dementia and Center for Neuro-Medicine, Brain Science Institute Korea Institute of Science and Technology, Seoul, Korea.|Biological Chemistry Program, Korea University of Science and Technology, Daejeon, Korea.
authors.forename: Sejin
authors.initials: S
authors.lastname: Lee
authors.affiliation: Convergence Research Center for Dementia and Center for Neuro-Medicine, Brain Science Institute Korea Institute of Science and Technology, Seoul, Korea.|Department of Biotechnology, Yonsei University, Seoul, Korea.
authors.forename: Seungyeop
authors.initials: S
authors.lastname: Baek
authors.affiliation: Convergence Research Center for Dementia and Center for Neuro-Medicine, Brain Science Institute Korea Institute of Science and Technology, Seoul, Korea.|Biological Chemistry Program, Korea University of Science and Technology, Daejeon, Korea.
authors.forename: Jiyoon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology Hanyang University, Ansan, Kyeonggi-do, Korea.
authors.forename: Hoyong
authors.initials: H
authors.lastname: Jung
authors.affiliation: Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology Hanyang University, Ansan, Kyeonggi-do, Korea.
authors.forename: Jung-Mi
authors.initials: JM
authors.lastname: Hah
authors.affiliation: Convergence Research Center for Dementia and Center for Neuro-Medicine, Brain Science Institute Korea Institute of Science and Technology, Seoul, Korea yskim@bio.kist.re.kr.|Biological Chemistry Program, Korea University of Science and Technology, Daejeon, Korea.
authors.forename: YoungSoo
authors.identifier: 0000-0001-5029-7082
authors.initials: Y
authors.lastname: Kim
mesh_terms: D061605:Administration, Intravenous; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D016923:Cell Death; D002540:Cerebral Cortex / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000503:physiopathology*; D006624:Hippocampus / Q000473:pathology*; D007093:Imidazoles / Q000008:administration & dosage / Q000378:metabolism*; D007211:Indoles / Q000008:administration & dosage / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000032:analysis; D016896:Treatment Outcome; D016875:tau Proteins / Q000032:analysis
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D007093:Imidazoles; D007211:Indoles; C558298:Mapt protein, mouse; D010750:Phosphoproteins; C507699:necrostatin-1; D016875:tau Proteins
keywords: Alzheimer's disease; Aβ aggregation; cognitive deficit; necrostatin‐1; tau hyperphosphorylation