Zebrafish Models of Neurodegenerative Disease Mechanisms

Zebrafish have emerged as versatile vertebrate models for dissecting the cellular and molecular mechanisms driving neurodegenerative diseases. Their optical transparency, rapid development and genetic tractability enable in vivo visualisation of neuronal populations and real-time assessment of pathological hallmarks such as protein aggregation, mitochondrial dysfunction and synaptic loss. Gene-editing technologies including CRISPR/Cas9 and antisense morpholinos facilitate the generation of transgenic and knockout lines that recapitulate key features of Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis. Dopaminergic neurons can be selectively labelled to monitor neurodegeneration in Parkinson-like models, while tau and amyloid reporters allow analysis of proteinopathy in Alzheimer’s paradigms. Zebrafish larvae support high-throughput chemical screens to identify small molecules that modulate autophagy, neuroinflammation and oxidative stress. Moreover, conservation of neurotransmitter systems and neuroimmune interactions in zebrafish affords insight into glial responses and cytokine-mediated toxicity. Beyond neuroscience, these models inform broader principles of neuronal survival and regenerative capacity, offering a platform for preclinical evaluation of neuroprotective agents. The scalability and cost-effectiveness of zebrafish studies accelerate target validation and therapeutic discovery, underscoring their global significance in addressing the unmet challenges of neurodegenerative disease.

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Zebrafish Models of Neurodegenerative Disease Mechanisms publication trend

The graph below shows the total number of articles in zebrafish models of neurodegenerative disease mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

CRISPR/Cas9: A genome-editing tool that introduces targeted DNA breaks to create gene knockouts or insertions.

Dopaminergic neuron: A nerve cell that produces dopamine, a neurotransmitter critical for motor control and reward pathways.

Microglia: Resident immune cells of the central nervous system that mediate inflammatory responses and clear debris.

Mitochondrial dysfunction: Impairment of cellular energy production and calcium homeostasis leading to neuronal vulnerability.

Autophagy: A cellular degradation process that recycles damaged organelles and protein aggregates to maintain neuronal health.

References

1. A zebrafish model of acmsd deficiency does not support a prominent role for ACMSD in Parkinson’s disease. npj Parkinson's Disease (2025).
2. Fish Models for Exploring Mitochondrial Dysfunction Affecting Neurodegenerative Disorders. International Journal of Molecular Sciences (2023).
3. Neuroprotective effects of Neurotrophin-3 in MPTP-induced zebrafish Parkinson’s disease model. Frontiers in Pharmacology (2023).