Behavioral Phenotyping and Pathological Indicators of Parkinson's Disease in C. elegans Models

Maulik, Malabika; Mitra, Swarup; Bult‐Ito, Abel; Taylor, Barbara; Vayndorf, Elena

doi:10.3389/fgene.2017.00077

Cited by 88 publications

(103 citation statements)

References 264 publications

(428 reference statements)

Supporting

Mentioning

101

Contrasting

Order By: Relevance

“…These cases have been associated with mutations in several genes, including α-synuclein, the vesicular trafficking protein VPS35, the multi-domain kinase LRRK2, and the mitochondrial stress response proteins PINK1, Parkin, and DJ-1. The C. elegans genome includes orthologues for most of these genes, except for α-synuclein [9,[20][21][22][23].…”

Section: Parkinson's Diseasementioning

confidence: 99%

“…As C. elegans has no orthologue of this protein, worm models have been generated by overexpression of wild-type or mutant forms of human α-synuclein in different tissues, i.e., either body-wall muscle, pan-neuronal, or only in the dopaminergic neurons. In most cases, overexpression leads to locomotion defects and the degeneration of dopaminergic neurons [9,[20][21][22][23].…”

Section: Parkinson's Diseasementioning

confidence: 99%

“…Further, in some cases, the effect of overexpression of the pathogenic mutant form of the human protein has been studied. For example, overexpression of a mutant form of human LRRK2 also induces age-dependent neurodegeneration in the worms [9,[20][21][22][23].…”

Section: Parkinson's Diseasementioning

confidence: 99%

“…Toxin-induced models of Parkinson's disease have also been developed by the administration to the worms of several neurotoxins, such as 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), rotenone, paraquat, or manganese [20,21,23]. The availability of C. elegans strains with different tissues or selected neuronal populations specifically labelled with fluorescent proteins or Ca 2+ sensors allows direct visualization of the changes in the cellular morphology or Ca 2+ dynamics induced by the toxins.…”

Section: Parkinson's Diseasementioning

confidence: 99%

See 3 more Smart Citations

The Role of Ca2+ Signaling in Aging and Neurodegeneration: Insights from Caenorhabditis elegans Models

Álvarez

Alvarez-Illera

García-Casas

et al. 2020

Cells

View full text Add to dashboard Cite

Ca2+ is a ubiquitous second messenger that plays an essential role in physiological processes such as muscle contraction, neuronal secretion, and cell proliferation or differentiation. There is ample evidence that the dysregulation of Ca2+ signaling is one of the key events in the development of neurodegenerative processes, an idea called the “calcium hypothesis” of neurodegeneration. Caenorhabditis elegans (C. elegans) is a very good model for the study of aging and neurodegeneration. In fact, many of the signaling pathways involved in longevity were first discovered in this nematode, and many models of neurodegenerative diseases have also been developed therein, either through mutations in the worm genome or by expressing human proteins involved in neurodegeneration (β-amyloid, α-synuclein, polyglutamine, or others) in defined worm tissues. The worm is completely transparent throughout its whole life, which makes it possible to carry out Ca2+ dynamics studies in vivo at any time, by expressing Ca2+ fluorescent probes in defined worm tissues, and even in specific organelles such as mitochondria. This review will summarize the evidence obtained using this model organism to understand the role of Ca2+ signaling in aging and neurodegeneration.

show abstract

Section: Parkinson's Diseasementioning

confidence: 99%

Section: Parkinson's Diseasementioning

confidence: 99%

Section: Parkinson's Diseasementioning

confidence: 99%

Section: Parkinson's Diseasementioning

confidence: 99%

See 2 more Smart Citations

The Role of Ca2+ Signaling in Aging and Neurodegeneration: Insights from Caenorhabditis elegans Models

Álvarez

Alvarez-Illera

García-Casas

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…After 30 min, the numbers of worms were scored in each quadrant. Ethanol avoidance index was calculated as the difference in number of worms in control quadrants versus in ethanol quadrants divided by the total number of worms (Cooper et al, 2015;Maulik et al, 2017) (n ≥ 30 worms/group per replicate).…”

Section: Ethanol Avoidance Assaymentioning

confidence: 99%

Downregulation of eEF1A/EFT3-4 Enhances Dopaminergic Neurodegeneration After 6-OHDA Exposure in C. elegans Model

2020

View full text Add to dashboard Cite

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the aggregation of α-synuclein protein and selective death of dopaminergic (DA) neurons in the substantia nigra of the midbrain. Although the molecular pathogenesis of PD is not completely understood, a recent study has reported that eukaryotic translation elongation factor 1 alpha (eEF1A) declined in the PD-affected brain. Therefore, the roles of eEF1A1 and eEF1A2 in the prevention of DA neuronal cell death in PD are aimed to be investigated. Herein, by using Caenorhabditis elegans as a PD model, we investigated the role of eft-3/eft-4, the worm homolog of eEF1A1/eEF1A2, on 6-hydroxydopamine (6-OHDA)-induced DA neuron degeneration. Our results demonstrated that the expressions of eft-3 and eft-4 were decreased in the 6-OHDA-induced worms. RNA interference (RNAi) of eft-3 and eft-4 resulted in dramatic exacerbation of DA neurodegeneration induced by 6-OHDA, as well as aggravated the food-sensing behavior, ethanol avoidance, and decreased lifespan when compared with only 6-OHDA-induced worms. Moreover, downregulation of eft-3/4 in 6-OHDA-induced worms suppressed the expression of the anti-apoptotic genes, including PI3K/age-1, PDK-1/pdk-1, mTOR/let-363, and AKT-1,2/akt-1,2, promoting the expression of apoptotic genes such as BH3/egl-1 and Caspase-9/ced-3. Collectively, these findings indicate that eEF1A plays an important role in the 6-OHDA-induced neurodegeneration through the phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase (Akt)/mammalian target of rapamycin (mTOR) pathway and that eEF1A isoforms may be a novel and effective pro-survival factor in protective DA neurons against toxin-induced neuronal death.

show abstract

The Effect of glna Loss on the Physiological and Pathological Phenotype of Parkinson's Disease C. elegans

Liang,

Zhao

2024

Clinical Laboratory Analysis

View full text Add to dashboard Cite

BackgroundParkinson's disease (PD) is a common neurodegenerative disease. Glutamate(Glu) excitotoxicity is one of the main pathogenesis of PD. Glutaminase (Gls) is an enzyme primarily responsible for catalyzing the hydrolysis and deamidation of glutamine (Gln) to produce Glu and ammonia. Inhibiting the function of Gls may have a beneficial effect on the treatment of PD by reducing the production of Glu. The homologous gene of Gls in C. elegans is glna.AimsTo explore the effects of glna loss on physiological and pathological phenotype of PD C. elegans, and to provide new ideas and references for the research and treatment of PD.Materials & MethodsWe used PD C. elegans UA44 and QIN27 to detect development and lifespan, behavior, degeneration of dopaminergic neurons, lipid levels, ROS levels, expression levels of common amino acids.ResultsGlna loss had no significant impact on the development and lifespan of PD C. elegans. Glna loss saved part of the decline of motor function, including the head thrash frequency and the body bend frequency, and the difference was significant. There was a trend of improvement in some motor behaviors, such as the ethanol avoidance experiment, while no improvement was observed in other experiments. Glna loss slowed down the degeneration of dopaminergic neurons. Glna loss increased the lipid levels and ROS levels in C. elegans. Glna loss decreased Glu content and increased Gln content in C. elegans.DiscussionThe effect of glna loss on PD C. elegans may be the result of multiple factors, such as the tissue types of α‐syn expression in C. elegans, the PD C. elegans model used, the adverse effects of glna loss on other systems, and the changes in ROS levels in C. elegans. The specific mechanisms causing these phenomena are still unclear and need to be further explored.ConclusionGlna loss has a certain protective effect on dopaminergic neurons in PD C. elegans, while the improvement effect on movement and behavior is limited.

show abstract

Behavioral Phenotyping and Pathological Indicators of Parkinson's Disease in C. elegans Models

Cited by 88 publications

References 264 publications

The Role of Ca2+ Signaling in Aging and Neurodegeneration: Insights from Caenorhabditis elegans Models

The Role of Ca2+ Signaling in Aging and Neurodegeneration: Insights from Caenorhabditis elegans Models

Downregulation of eEF1A/EFT3-4 Enhances Dopaminergic Neurodegeneration After 6-OHDA Exposure in C. elegans Model

The Effect of glna Loss on the Physiological and Pathological Phenotype of Parkinson's Disease C. elegans

Contact Info

Product

Resources

About