RESEARCH

Scientific Overview

For most neurodegenerative diseases, no effective drug is currently available. The major pathogenic hallmarks of neurodegenerative diseases include the aggregation and deposition of abnormal protein, which lead to neuritic dystrophy, synapse loss, microgliosis, astrogliosis, and cognitive impairment. Another major pathological feature of neurological diseases is energy dysfunction associated with mitochondrial impairment and reduced ATP production.

To develop new therapeutic strategies, our team has successfully synthesized and optimized a new chemical entity, J4, with a novel MOA that can be used to treat neurodegenerative diseases including Alzheimer’s disease (AD) by targeting the dysregulated nucleoside homeostasis in the brain. Through preclinical studies, the results show that J4 modulates nucleoside homeostasis and subsequently ameliorates neuronal energy failure. Our data suggest that J4 exhibits superior profiles in pharmacology (i.e., the rescue of cognitive decline in three AD mouse models). In addition, it is shown that the novel MOA can be applied for the treatment of neurodegenerative diseases including AD, as well as the mild cognitive impairment in aging process.