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REVIEW ARTICLE
Parkinson’s disease in a dish: The emerging role of

organoids in research and therapy

Siyue Qin, Ju Gao, Mao Ding, Lauren H. Vicuna, and Xinglong Wang*
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, Arizona, United States of America
*Corresponding author: Xinglong Wang (xlwang@arizona.edu)

Citation: Qin S, Gao J, Ding M, Abstract
Vicuna LH, Wang, X. Parkinson’s
disease in a dish: The emerging role
of organoids in research and therapy. Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked
Organoid Res. 2025;1(2):025040006. by the degeneration of dopaminergic (DA) neurons in the substantia nigra
doi: 10.36922/OR025040006 and the accumulation of α-synuclein aggregates, leading to motor and non-
Received: January 24, 2025 motor dysfunctions. The pathogenesis of PD involves a complex interplay of
genetic mutations, environmental factors, and cellular mechanisms, including
Revised: March 7, 2025
mitochondrial dysfunction, impaired proteostasis, neuroinflammation, and gut-
Accepted: March 14, 2025 brain axis dysregulation. Traditional research models, such as animal models and
Published online: April 16, 2025 two-dimensional cell cultures, have provided valuable insights but often fall short
in replicating the multifaceted and progressive nature of PD, especially in sporadic
Copyright: © 2025 Author(s).
This is an Open-Access article cases. The emergence of organoid technology offers a transformative approach to
distributed under the terms of the PD research. This technology enables the generation of three-dimensional structures
Creative Commons Attribution that closely mimic the architecture, cellular composition, and functionality of the
License, permitting distribution, and
reproduction in any medium, which human midbrain. Midbrain organoids have become pivotal models for investigating
provided that the original work is disease mechanisms, including DA neuron degeneration, α-synuclein aggregation,
properly cited. and neuroinflammatory responses. Moreover, organoids enable high-throughput
Publisher’s Note: AccScience drug screening and the identification of potential therapeutic targets. Beyond
Publishing remains neutral with regard modeling, recent advancements have demonstrated the feasibility of organoid
to jurisdictional claims in published
maps and institutional affiliations. transplantation as a therapeutic strategy. This review summarizes the current
progression of organoid technology in PD research, focusing on its application in
modeling pathomechanisms, drug discovery, and therapeutic applications. Despite
being in its early stages, organoid technology holds significant promise for advancing
our understanding of PD pathogenesis and developing translational therapies.

Keywords: Parkinson’s disease; Organoids; α-synuclein; Midbrain dopaminergic
neurons; Drug screen; Organoid transplantation; Neurodegeneration

1. Introduction to sporadic cases. Clinically, PD presents with motor
2
symptoms such as tremors, rigidity, bradykinesia, and
Parkinson’s disease (PD), first detailed by James Parkinson postural instability, alongside non-motor issues such as
in 1817, is a progressive neurodegenerative disorder cognitive decline, sleep disturbances, and autonomic
1
characterized by the degeneration of dopaminergic (DA) dysfunction. 3
neurons in the substantia nigra and the accumulation of
α-synuclein aggregates, known as Lewy bodies. These The pathogenesis of PD is driven by a complex network
pathological changes disrupt motor control and contribute of cellular and molecular dysfunctions. A hallmark feature
to non-motor symptoms. Genetic mutations, including of PD is the progressive degeneration of DA neurons
those in the leucine-rich repeat kinase 2 (LRRK2), SNCA, in the substantia nigra, leading to dopamine depletion
4
PARK7, PTEN-induced kinase 1 (PINK1), and PRKN genes, in the striatum and subsequent motor deficits. This
play significant roles in familial PD, while environmental neurodegeneration is accompanied by the accumulation of
factors, such as pesticide exposure and aging, contribute α-synuclein aggregates in the form of Lewy bodies and Lewy

Volume 1 Issue 2 (2025) 1 doi: 10.36922/OR025040006