Use of Amplified Lewy Body Dementia Fibrils and Autoradiography to Characterize Binding of Radioligand Tg-1-90B to Alpha-Synuclein Fibrils in Postmortem Brain Tissue.

ABSTRACT: Parkinson's disease (PD) and Lewy Body Dementia (LBD) are defined by accumulation of alpha-synuclein (Asyn) fibrils within Lewy bodies (LBs) and Lewy neurites (LNs). The development of a Positron Emission Tomography (PET) tracer for quantifying Asyn fibrils would improve diagnostic accuracy and provide a biomarker for disease progression. We previously described radioligand [³H]Tg-1-90B, which binds to in vitro Asyn fibrils (PDB 2N0A) via interactions with residues Y39, S42 and K44. Here, we performed molecular docking studies with Tg1-90B and PD/LBD Asyn fibrils (PDB 8A9L), which predicts interactions with residues Y39 and K43 in a structurally distinct binding site. In radioligand binding assays, Tg-1-90B has moderate to high affinity (K_d 17.5 nM) for amplified LBD

SUBMITTER: O'Shea JY 

PROVIDER: S-EPMC12468313 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature