Modeling Environmentally-Induced Motor Neuron Degeneration in Zebrafish

Morrice, Jessica R.; Gregory‐Evans, Cheryl Y.; Shaw, Christopher A.

doi:10.1038/s41598-018-23018-w

Cited by 42 publications

(27 citation statements)

References 67 publications

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“…A novel variant in UBQLN4 compromises motor axon morphogenesis in zebrafish, impairing the proteasomal function (Edens et al, 2017;Morrice et al, 2018). Based on these reports, the clearance of junk protein is important in the compartment of the MN axon.…”

Section: Clearance Of Junk Proteinmentioning

confidence: 99%

Omics Approach to Axonal Dysfunction of Motor Neurons in Amyotrophic Lateral Sclerosis (ALS)

et al. 2020

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Amyotrophic lateral sclerosis (ALS) is an intractable adult-onset neurodegenerative disease that leads to the loss of upper and lower motor neurons (MNs). The long axons of MNs become damaged during the early stages of ALS. Genetic and pathological analyses of ALS patients have revealed dysfunction in the MN axon homeostasis. However, the molecular pathomechanism for the degeneration of axons in ALS has not been fully elucidated. This review provides an overview of the proposed axonal pathomechanisms in ALS, including those involving the neuronal cytoskeleton, cargo transport within axons, axonal energy supply, clearance of junk protein, neuromuscular junctions (NMJs), and aberrant axonal branching. To improve understanding of the global changes in axons, the review summarizes omics analyses of the axonal compartments of neurons in vitro and in vivo, including a motor nerve organoid approach that utilizes microfluidic devices developed by this research group. The review also discusses the relevance of intra-axonal transcription factors frequently identified in these omics analyses. Local axonal translation and the relationship among these pathomechanisms should be pursued further. The development of novel strategies to analyze axon fractions provides a new approach to establishing a detailed understanding of resilience of long MN and MN pathology in ALS.

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Section: Clearance Of Junk Proteinmentioning

confidence: 99%

Omics Approach to Axonal Dysfunction of Motor Neurons in Amyotrophic Lateral Sclerosis (ALS)

et al. 2020

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“…Studies of microglial behavior in fish are becoming increasingly popular ( Table 1 ), particularly those focused on the microglial response to injury via phagocytosis [ 50 , 52 , 143 ] and neuronal degeneration [ 144 , 145 , 146 ]. The phagocytic behavior of immune cells is potentially important in the establishment of new connections in the brain, as degenerating connections first must be removed before new connections can form [ 147 ].…”

Section: Macrophages and Microglia In Tissue Regeneration In Fishmentioning

confidence: 99%

Role of Macrophages and Microglia in Zebrafish Regeneration

Var

Byrd-Jacobs

2020

IJMS

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Currently, there is no treatment for recovery of human nerve function after damage to the central nervous system (CNS), and there are limited regenerative capabilities in the peripheral nervous system. Since fish are known for their regenerative abilities, understanding how these species modulate inflammatory processes following injury has potential translational importance for recovery from damage and disease. Many diseases and injuries involve the activation of innate immune cells to clear damaged cells. The resident immune cells of the CNS are microglia, the primary cells that respond to infection and injury, and their peripheral counterparts, macrophages. These cells serve as key modulators of development and plasticity and have been shown to be important in the repair and regeneration of structure and function after injury. Zebrafish are an emerging model for studying macrophages in regeneration after injury and microglia in neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease. These fish possess a high degree of neuroanatomical, neurochemical, and emotional/social behavioral resemblance with humans, serving as an ideal simulator for many pathologies. This review explores literature on macrophage and microglial involvement in facilitating regeneration. Understanding innate immune cell behavior following damage may help to develop novel methods for treating toxic and chronic inflammatory processes that are seen in trauma and disease.

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“…BPA is an industrial plasticizer which is thought to be a potential trigger in ALS pathogenesis. It can cause motor neuron degeneration, affect locomotor activity, reduce neuromuscular junction (NMJ) integrity and motor neuron-specific cell death in zebrafish embryos (Morrice et al, 2018b). BMAA is a nonproteinogenic neurotoxic amino acid produced by cyanobacteria.…”

Section: Neurotoxic Zebrafish Models Of Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Advances of Zebrafish in Neurodegenerative Disease: From Models to Drug Discovery

Wang

Zhang

et al. 2021

Front. Pharmacol.

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Neurodegenerative disease (NDD), including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, are characterized by the progressive loss of neurons which leads to the decline of motor and/or cognitive function. Currently, the prevalence of NDD is rapidly increasing in the aging population. However, valid drugs or treatment for NDD are still lacking. The clinical heterogeneity and complex pathogenesis of NDD pose a great challenge for the development of disease-modifying therapies. Numerous animal models have been generated to mimic the pathological conditions of these diseases for drug discovery. Among them, zebrafish (Danio rerio) models are progressively emerging and becoming a powerful tool for in vivo study of NDD. Extensive use of zebrafish in pharmacology research or drug screening is due to the high conserved evolution and 87% homology to humans. In this review, we summarize the zebrafish models used in NDD studies, and highlight the recent findings on pharmacological targets for NDD treatment. As high-throughput platforms in zebrafish research have rapidly developed in recent years, we also discuss the application prospects of these new technologies in future NDD research.

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Modeling Environmentally-Induced Motor Neuron Degeneration in Zebrafish

Cited by 42 publications

References 67 publications

Omics Approach to Axonal Dysfunction of Motor Neurons in Amyotrophic Lateral Sclerosis (ALS)

Omics Approach to Axonal Dysfunction of Motor Neurons in Amyotrophic Lateral Sclerosis (ALS)

Role of Macrophages and Microglia in Zebrafish Regeneration

Advances of Zebrafish in Neurodegenerative Disease: From Models to Drug Discovery

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