Heparan sulfate proteoglycans mediate prion-like α-synuclein toxicity in Parkinson's in vivo models

Merry Chen, Julie Vincent, Alexis Ezeanii, Saurabh Wakade, Shobha Yerigenahally, Danielle E. Mor

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by progressive motor decline and the aggregation of α-synuclein protein. Growing evidence suggests that α-synuclein aggregates may spread from neurons of the digestive tract to the central nervous system in a prion-like manner, yet the mechanisms of α-synuclein transmission and neurotoxicity remain poorly understood. Animal models that are amenable to high-throughput investigations are needed to facilitate the discovery of disease mechanisms. Here we describe the first Caenorhabditis elegans models in which feeding with α-synuclein preformed fibrils (PFFs) induces dopaminergic neurodegeneration, prion-like seeding of aggregation of human α-synuclein expressed in the host, and an associated motor decline. RNAi-mediated knockdown of the C. elegans syndecan sdn-1, or other enzymes involved in heparan sulfate proteoglycan synthesis, protected against PFF-induced α-synuclein aggregation, motor dysfunction, and dopamine neuron degeneration. This work offers new models by which to investigate gut-derived α-synuclein spreading and propagation of disease.

Original languageEnglish (US)
JournalLife Science Alliance
Issue number11
StatePublished - Nov 1 2022

ASJC Scopus subject areas

  • Ecology
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Plant Science
  • Health, Toxicology and Mutagenesis


Dive into the research topics of 'Heparan sulfate proteoglycans mediate prion-like α-synuclein toxicity in Parkinson's in vivo models'. Together they form a unique fingerprint.

Cite this