Modeling the Progression of Cardiac Catecholamine Deficiency in Lewy Body Diseases.

ABSTRACT: Background Lewy body diseases (LBDs) feature deficiency of the sympathetic neurotransmitter norepinephrine in the left ventricular myocardium and sympathetic intra-neuronal deposition of the protein alpha-synuclein (αS). LBDs therefore are autonomic synucleinopathies. Computational modeling has revealed multiple functional abnormalities in residual myocardial sympathetic noradrenergic nerves in LBDs, including decreased norepinephrine synthesis, vesicular storage, and recycling. We report an extended model that enables predictions about the progression of LBDs and effects of genetic predispositions and treatments on that progression. Methods and Results The model combines cardiac sympathetic activation with autotoxicity mediated by the dopamine metabolite 3,4-dihydroxyphenylacetaldehyde. W

SUBMITTER: Goldstein DS 

PROVIDER: S-EPMC9238705 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature