Knockdown of heterochromatin protein 1 binding protein 3 recapitulates phenotypic, cellular, and molecular features of aging.

ABSTRACT: Identifying genetic factors that modify an individual's susceptibility to cognitive decline in aging is critical to understanding biological processes involved and mitigating risk associated with a number of age-related disorders. Recently, heterochromatin protein 1 binding protein 3 (Hp1bp3) was identified as a mediator of cognitive aging. Here, we provide a mechanistic explanation for these findings and show that targeted knockdown of Hp1bp3 in the hippocampus by 50%-75% is sufficient to induce cognitive deficits and transcriptional changes reminiscent of those observed in aging and Alzheimer's disease brains. Specifically, neuroinflammatory-related pathways become activated following Hp1bp3 knockdown in combination with a robust decrease in genes involved in synaptic activity and neuron

SUBMITTER: Neuner SM 

PROVIDER: S-EPMC6351847 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature