Design and evaluation of bi-functional iron chelators for protection of dopaminergic neurons from toxicants.

ABSTRACT: While the etiology of non-familial Parkinson's disease (PD) remains unclear, there is evidence that increased levels of tissue iron may be a contributing factor. Moreover, exposure to some environmental toxicants is considered an additional risk factor. Therefore, brain-targeted iron chelators are of interest as antidotes for poisoning with dopaminergic toxicants, and as potential treatment of PD. We, therefore, designed a series of small molecules with high affinity for ferric iron and containing structural elements to allow their transport to the brain via the neutral amino acid transporter, LAT1 (SLC7A5). Five candidate molecules were synthesized and initially characterized for protection from ferroptosis in human neurons. The promising hydroxypyridinone SK4 was characterized further. S

SUBMITTER: Gutbier S 

PROVIDER: S-EPMC7415766 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature