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.
Bibliographical noteFunding Information:
This research was supported by National Research Council of Science & Technology (NST, CRC-15-04-KIST), Basic Science Research Program through the National Research Foundation of Korea (NRF, 2015R1A6A3A04058568 and 2014R1A1A3051648) funded by the Ministry of Education, Science and Technology, and Korea Institute of Science and Technology (KIST Young Fellowship, 2V05030). The authors thank Mr. Yakdol Cho (Korea Institute of Science and Technology) for animal maintenance and preparation; Dr. Yun Kyung Kim (Korea Institute of Science and Technology) and Dr. Sungsu Lim (Korea Institute of Science and Technology) for preparation of tau aggregation; Mr. Juhyeong Jo (GE Healthcare Korea/Japan) for Biacore analyses; and Ms. Sarah Hesse (University of Glasgow) for editing advices. The authors appreciate Dr. Hye Yun Kim for scientific advices.
All Science Journal Classification (ASJC) codes
- Molecular Medicine