Microengineering of the capillary interface of midbrain dopaminergic neurons to study Parkinson's disease vascular alterations.
Microengineering of the capillary interface of midbrain dopaminergic neurons to study Parkinson's disease vascular alterations.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Binghamton, US · Author affiliation
Department of Electrical and Computer Engineering, Binghamton University, Binghamton, NY, USA.Location evidence
Philadelphia, US · Author affiliation
Department of Chemistry, Drexel University, Philadelphia, PA, USA.Location evidence
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Original abstract
Parkinson's Disease (PD) involves not only α-synuclein pathology in dopaminergic neurons but also vascular impairments that remain underexplored due to limitations of traditional in vitro models. Here we present a microengineered 3D neurovascular midbrain model that reconstructs the capillary interface of substantia nigra dopaminergic neurons. In our proof-of-concept demonstration, we successfully recapitulated neuronal pathology in PD, including α-synuclein aggregation, inflammatory responses, and progressive neuronal degeneration, by exposing our model to specially generated PD-associated α-synuclein preformed-fibrils. Importantly, this engineering approach also enables the investigation of progressive vascular abnormalities in PD, such as endothelial dysfunction, barrier disruption, vascular regression, and the resulting impairment of blood flow. Our PD model establishes a tractable platform for investigating the multifaceted nature of the disease and understanding the complex interplay between neurodegeneration and vascular pathology, offering a unique tool for developing innovative therapeutic strategies that address both the neuronal and vascular components of PD pathology.