Nec-1 alleviates cognitive impairment with reduction of A? 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-? (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.

SUBMITTER: Yang SH 

PROVIDER: S-EPMC5210088 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature