Targeting synaptic dysfunction in dementia

Dementia is a global burden with devastating effects on cognition and emotional regulation. Tau protein is a key driver, and its dysfunction in major brain circuits including the hippocampus, the entorhinal cortex, and the amygdala correlates with synaptic decline, leading to cognitive and emotional symptoms. However, the underlying molecular mechanisms remain poorly understood, and the potential for therapeutic intervention targeting these pathways is yet to be explored. This project aims to bridge this gap by identifying synaptic mechanisms of Tau-induced connectivity dysfunction and by developing therapeutic strategies to mitigate its effects based on Tau knock-in models, advanced and innovative cell-specific synaptic screenings, insights from hibernating hamsters, and patient brain material. Our team’s preliminary data already reveal promising targets and Tau-induced synaptic changes correlating with behavioral alterations, giving us a head-start. This proposal is driven by a strong consortium, collaborating with top-tier experts, to integrate cutting-edge molecular and cellular analyses with preclinical therapeutic development.

Keywords:preclinical model, Tau, antisense oligonucleotide, connectivity, dementia, emotional dysfunction, cognitive decline, synapse

Disciplines:Animal cell and molecular biology, Neurological and neuromuscular diseases, Cell signalling, Behavioural neuroscience