The dopamine receptor agonist apomorphine stabilizes neurotoxic α-synuclein oligomers. Academic Article uri icon

Overview

abstract

  • The misfolding and aggregation of the protein α-synuclein (aSyn) into potentially neurotoxic oligomers is believed to play a pivotal role in the neuropathogenesis of Parkinson's disease (PD). Herein, we explore how apomorphine (Apo), a nonselective dopamine D1 and D2 receptor agonist utilized in the therapy for PD, affects the aggregation and toxicity of aSyn in vitro. Our data indicated that Apo inhibits aSyn fibrillation leading to the formation of large oligomeric species (Apo-aSyn-O), which exhibit remarkable toxicity in mesencephalic dopaminergic neurons in primary cultures. Interestingly, purified Apo-aSyn-O, even at very low concentrations, seems to be capable of converting unmodified aSyn monomer into neurotoxic species. Collectively, our findings warn for a possible dangerous effect of Apo on aSyn misfolding/aggregation pathway.

publication date

  • December 29, 2021

Research

keywords

  • alpha-Synuclein

Identity

PubMed Central ID

  • PMC8972942

Scopus Document Identifier

  • 85122068397

Digital Object Identifier (DOI)

  • 10.1002/1873-3468.14263

PubMed ID

  • 34928512

Additional Document Info

volume

  • 596

issue

  • 3