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<p>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.</p>

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Microengineering of the capillary interface of midbrain dopaminergic neurons to study Parkinson’s disease vascular alterations

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月10日

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  • Anika Alim,
  • Yoongyeong Baek,
  • Myungwoon Lee,
  • Jungwook Paek

摘要

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.