Fish Models for Exploring Mitochondrial Dysfunction Affecting Neurodegenerative Disorders

Abstract

Neurodegenerative disorders are characterized by the progressive loss of neuronal structure or function, resulting in memory loss and movement disorders. Although the detailed pathogenic mechanism has not been elucidated, it is thought to be related to the loss of mitochondrial function in the process of aging. Animal models that mimic the pathology of a disease are essential for understanding human diseases. In recent years, small fish have become ideal vertebrate models for human disease due to their high genetic and histological homology to humans, ease of in vivo imaging, and ease of genetic manipulation. In this review, we first outline the impact of mitochondrial dysfunction on the progression of neurodegenerative diseases. Then, we highlight the advantages of small fish as model organisms, and present examples of previous studies regarding mitochondria-related neuronal disorders. Lastly, we discuss the applicability of the turquoise killifish, a unique model for aging research, as a model for neurodegenerative diseases. Small fish models are expected to advance our understanding of the mitochondrial function in vivo, the pathogenesis of neurodegenerative diseases, and be important tools for developing therapies to treat diseases.

Keywords: medaka; mitochondria; neurodegenerative disorders; turquoise killifish; zebrafish.

Figure 1

Multifactorial effects of mitochondrial dysfunction in the process of neurodegenerative disorders.

Figure 2

Schematic image of oxidative phosphorylation (OXPHOS) process and reactive oxygen species (ROS) production.

Figure 3

Advantages and applications of small fish models.

Figure 4

Progenitor cells (radial glial cells) distribution in the mouse and zebrafish brain. The red color indicates regions of constitutive proliferation. Based on the data summary from [295]. SVZ, subventricular zone; SGZ, dentate gyrus subgranular zone.