Yang, Seung-Hoon Lee, Dongkeun Kenneth Shin, Jisu Lee, Sejin Baek, Seungyeop Kim, Jiyoon Jung, Hoyong Hah, Jung-Mi Kim, YoungSoo 2024-01-20T02:32:25Z 2024-01-20T02:32:25Z 2021-09-05 2017-01 1757-4676 https://pubs.kist.re.kr/handle/201004/123248 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- (A) and hyperphosphorylation of tau. Here, we found that an anti-necroptotic molecule necrostatin-1 (Nec-1) directly targets A 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 A oligomers, plaques and hyperphosphorylated tau without affecting production of A, 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. English WILEY BETA-AMYLOID PEPTIDE ALZHEIMERS-DISEASE A-BETA MOUSE MODEL CELL-DEATH HYPOTHETICAL MODEL DIFFUSE PLAQUES BRAIN ATROPHY CROSS-LINKING IN-VIVO Nec-1 alleviates cognitive impairment with reduction of A and tau abnormalities in APP/PS1 mice Article 10.15252/emmm.201606566 1 EMBO MOLECULAR MEDICINE, v.9, no.1, pp.61 - 77 EMBO MOLECULAR MEDICINE 9 1 61 77 scie scopus 000392431800006 2-s2.0-85006065082 Medicine, Research & Experimental Research & Experimental Medicine Article BETA-AMYLOID PEPTIDE ALZHEIMERS-DISEASE A-BETA MOUSE MODEL CELL-DEATH HYPOTHETICAL MODEL DIFFUSE PLAQUES BRAIN ATROPHY CROSS-LINKING IN-VIVO Alzheimer&apos s disease A aggregation cognitive deficit necrostatin-1 tau hyperphosphorylation