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Brain Organoids as Emerging Platforms for Modeling Neurodegenerative Diseases: Progress, Challenges, and Future
Yesim Kaya1, Kevser Kübra Kırboğa2
1Department of Molecular Biology and Genetics, Faculty of Science, Mugla Sitki Kocman University, Mugla, Turkey.
Journal of Neurochemistry
|March 5, 2026
Summary
Three-dimensional (3D) brain organoids model neurodegenerative diseases by recapitulating human brain conditions. While offering insights into disease mechanisms and drug screening, limitations like incomplete maturation persist.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Disease Modeling
Background:
- Neurodegenerative diseases (e.g., Alzheimer's, Parkinson's) are a growing global health burden, particularly affecting aging populations.
- Conventional models (2D cultures, animal models) fail to fully replicate the human brain's complex cellular and molecular pathology.
- Three-dimensional (3D) brain organoids offer a more physiologically relevant model, mimicking human brain conditions.
Purpose of the Study:
- To review the advantages and disadvantages of using 3D brain organoids for modeling neurodegenerative diseases.
- To highlight the potential of brain organoids as a bridge from bench to bedside for therapeutic development.
- To provide a contemporary perspective on brain organoid technology in neurodegenerative disease research.
Main Methods:
- Utilizing human induced pluripotent stem cells (iPSCs) to generate 3D brain organoids.
- Employing brain organoids to study molecular and genetic mechanisms of neurodegenerative diseases.
- Leveraging brain organoids for in vitro disease modeling and drug screening.
Main Results:
- Brain organoids exhibit key features of neurodegenerative diseases, including neuronal-glial interactions, self-organization, protein aggregation, neuroinflammation, and degeneration.
- These organoids provide novel insights into disease mechanisms and serve as platforms for therapeutic discovery.
- Current limitations include incomplete tissue maturation, lack of vascularization, and limited cellular diversity.
Conclusions:
- 3D brain organoids represent a powerful tool for advancing the understanding and treatment of neurodegenerative diseases.
- Despite current limitations, brain organoids hold significant promise for personalized medicine and drug development.
- Continued research is essential to overcome existing challenges and fully realize the potential of brain organoid technology.
