The Promise of the Zebrafish Model for Parkinson’s Disease: Today’s Science and Tomorrow’s Treatment

Abstract

The second most prevalent neurodegenerative disorder in the elderly is Parkinson’s disease (PD). Its etiology is unclear and there are no available disease-modifying medicines. Therefore, more evidence is required concerning its pathogenesis. The use of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is the basis of most animal models of PD. MPTP is metabolized by monoamine oxidase B (MAO B) to MPP + and induces the loss of dopaminergic neurons in the substantia nigra in mammals. Zebrafish have been commonly used in developmental biology as a model organism, but owing to its perfect mix of properties, it is now emerging as a model for human diseases. Zebrafish (Danio rerio) are cheap and easy to sustain, evolve rapidly, breed transparent embryos in large amounts, and are readily manipulated by different methods, particularly genetic ones. Furthermore, zebrafish are vertebrate species and mammalian findings obtained from zebrafish may be more applicable than those derived from genetic models of invertebrates such as Drosophila melanogaster and Caenorhabditis elegans. The resemblance cannot be taken for granted, however. The goal of the present review article is to highlight the promise of zebrafish as a PD animal model. As its aminergic structures, MPTP mode of action, and PINK1 roles mimic those of mammalians, zebrafish seems to be a viable model for studying PD. The roles of zebrafish MAO, however, vary from those of the two types of MAO present in mammals. The benefits unique to zebrafish, such as the ability to perform large-scale genetic or drug screens, should be exploited in future experiments utilizing zebrafish PD models.

Comparison of the effect of rotenone and 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine on inducing chronic Parkinson's disease in mouse models

“…In DA neurons, MPP + accumulates in the mitochondria, synaptic vesicles and cytoplasm; a part of the accumulated MPP + inhibits mitochondrial complex I ( 21 ). Although their mechanisms of action are not entirely understood, MPTP and rotenone both effectively induce PD-like symptoms ( 22 ).…”

Zebrafish Is a Powerful Tool for Precision Medicine Approaches to Neurological Disorders

“…Thus, target identification is critical in this process, and selecting a relevant target requires a greater understanding of the disease’s pathophysiology and molecular process ( Gashaw et al, 2012 ). As zebrafish have been successful in mimicking a plethora of neurological disorders ( Ramesh et al, 2010 ; Khan et al, 2017 ; Fontana et al, 2018 ; Gawel et al, 2020 ; Razali et al, 2021 ; Wang et al, 2021 ), it can pave the way for the discovery of such novel drug targets. One classical approach to target identification in zebrafish has been the use of morpholino-oligonucleotides but as said previously, their popularity and the confidence in their specificity has declined.…”

Fish Behavior as a Neural Proxy to Reveal Physiological States

“…Zebrafish and medaka have been used as models to investigate the etiology and pathophysiology of Parkinson’s disease (PD). Typically, there are two types of PD models: neurotoxin-induced and gene-based models to reduce dopaminergic neurons and dopamine release to mimic corresponding PD symptoms ( Lam et al, 2005 ; McKinley et al, 2005 ; Matsui et al, 2012 ; Vaz et al, 2018 ; Najib et al, 2020 ; Razali et al, 2021 ). PD model fish also showed locomotion deficits, including a reduction in the swimming speed, an increase in the no-moving time, and impairment of touch sensations, which are similar to symptoms of PD patients ( Lam et al, 2005 ; Milanese et al, 2012 ; Hughes et al, 2020 ; Robea et al, 2020 ; Wasel and Freeman, 2020 ).…”