Benzoxazole ligands target α-synuclein aggregates as candidate PET tracer scaffolds
- A benzoxazole-based ligand series was identified through a surface plasmon resonance screen aimed at α-synuclein aggregates, the central pathology in Parkinson's disease.
- Two leads, D15 and D16, bound the aggregates strongly in vitro and were active in SH-SY5Y cells and in brain tissue from PFF-injected mice.
- Both discriminated well against tau and amyloid-beta aggregates in transgenic mouse sections; good brain penetration and radiolabel-friendly structures make them PET starting points.
💡 Points
Discrimination against tau and Aβ in transgenic sections is the number that matters for an α-syn PET tracer, since mixed pathology in real brains is where tracers fall apart. But SPR on recombinant aggregates and PFF mouse tissue says little about Lewy body or MSA fibril polymorphs. I'd want Kd against patient-derived material and off-target binding (MAO, amyloid) before calling these a scaffold.