Topic: 5xFAD

Several therapeutic targets have been identified to counteract the cognitive decline of Alzheimer's disease (AD). One of the recent approaches, which takes account the multifactorial origin of AD, is pleiotropic drugs. Multi-targeted directed ligands are designed to target different molecular causes involved in the pathogenesis of AD. A novel compound, acting as a prodrug and able of both selectively inhibiting butyrylcholinesterase and secondarily interacting with serotonin subtype 4 receptor, has therefore been developed. The first step of the project was to assess pharmacological screening

Synaptic dysfunction is an early hallmark of AD pathology. It is characterized by the disruption of synaptic transmission and plasticity. Endosomal trafficking is central to this process. The retromer complex orchestrates the movement of vesicle contents, either pushing them back to the Golgi, degrading them, or recycling them to the plasma membrane. Variations in the cargo recognition component of the retromer, VPS35, have been associated with both Parkinson's (D620N mutation, PARK17) and Alzheimer's (L625P mutation). Extensive pathophysiological studies have been conducted on Parkinson's dis