Synucleinopathies, including Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB), are among the most prevalent neurodegenerative disorders globally. These disorders are caused by the accumulation of aggregated protein α-synuclein (α-syn) in the brain. Predictable spread of α-syn pathology in PD and DLB patients and animal models suggest α-syn propagates between synaptically interconnected brain regions and underlies disease progression. In vitro, α-syn aggregates transmit neuron-to-neuron trans-synaptically, via tunneling nanotubes or by release and uptake processes. Mounting evidence suggests that extracellular α-syn exerts a key role in the progression of syn pathology and that α-syn pathogenesis is not only a self-contained cellular phenomenon, but also an extracellular event. Heparan sulfate proteoglycans (HSPGs) are integral components of the neuronal glycocalyx and synapses where they interact with α-syn aggregates, modulating their internalization, aggregation and toxicity in cell culture. Our laboratory aims to define the role of heparan sulfate suring synuclein pathology.
