Stabilization and Reduced Cytotoxicity of Amyloid Beta Aggregates in the Presence of Catechol Neurotransmitters

Neurochem Res. 2023 Oct 17. doi: 10.1007/s11064-023-04036-1. Online ahead of print.ABSTRACTOligomeric aggregates of the amyloid-beta (Aβ) peptide have been implicated as the toxic species for Alzheimer's disease by contributing to oxidative cytotoxicity and physical disruption in cell membranes in the brain. Recent evidence points to the ability of the catecholamine neurotransmitter dopamine in the presence of copper ions to both stabilize oligomers and decrease the toxic effects of these oligomers. Based on these results, physical characterization of aggregates and subsequent cell studies with a neuroblastoma line were performed that show both dopamine and the related neurotransmitter, norepinephrine, can stabilize oligomers and decrease toxicity of Aβ aggregates without copper present. To investigate this reduction of toxicity, structural characterization of oligomers in the presence of neurotransmitters was compared to aggregates formed with Aβ alone. Gel electrophoresis and transmission electron microscopy show higher levels of oligomers in the presence of dopamine and norepinephrine, yet the oligomer structure is largely amorphous. Aβ aggregated alone forms the predicted highly organized fibrillar species, with increased levels of dityrosine covalent linkages, which are largely absent in the presence of the neurotransmitters. A proposed mechanism for the observed decrease in cell death by Aβ in the presence of dopamine and norepinephrine suggests the neurotransmitte...
Source: Neurochemical Research - Category: Neuroscience Authors: Source Type: research