Preclinical Evaluation of a Novel Molecule Targeting Nucleoside Homeostasis to Restore Energy Metabolism and Cognitive Function in Alzheimer's Disease.

ABSTRACT: Alzheimer's disease (AD) is the most prevalent cause of dementia, characterized by progressive cognitive decline and cerebral metabolic impairment. Yet, the therapeutic options for addressing the disease pathogenesis are limited. Here, we report an approach by targeting brain nucleoside homeostasis and energy metabolism to alleviate AD-associated cognitive deficits. A compound, J4, was designed to modulate nucleoside homeostasis by interacting with the equilibrative nucleoside transporter-1 (ENT1). The effects of J4 on brain nucleoside homeostasis and energy metabolism were examined in mice. Two AD animal models, THY-Tau22 and APP/PS1 mice, were used to evaluate the translational potential of J4 for the treatment of AD. Cognitive function and functional ability were assessed using the Morr

SUBMITTER: Wu KC 

PROVIDER: S-EPMC12496225 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature