A Two-Clone Approach to Study Signaling Interactions among Neuronal Cells in a Pre-clinical Alzheimer's Disease Model

Yeates, Catherine J.; Sarkar, Ankita; Deshpande, Prajakta; Kango‐Singh, Madhuri; Singh, Amit

doi:10.1016/j.isci.2020.101823

Cited by 10 publications

(9 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Statistical analysis was performed using student’s t-test for independent samples. Sample size used for the calculation was five in number (n = 5), otherwise specified ( Mehta et al., 2019 ; Raj et al., 2020 ; Yeates et al., 2020 ). Statistical significance was determined with 95% confidence (p < 0.05).…”

Section: Methodsmentioning

confidence: 99%

Newt regeneration genes regulate Wingless signaling to restore patterning in Drosophila eye

et al. 2021

Self Cite

View full text Add to dashboard Cite

Summary Newts utilize their unique genes to restore missing parts by strategic regulation of conserved signaling pathways. Lack of genetic tools poses challenges to determine the function of such genes. Therefore, we used the Drosophila eye model to demonstrate the potential of 5 unique newt ( Notophthalmus viridescens ) gene(s), viropana1-viropana5 ( vna1-vna5 ), which were ectopically expressed in L 2 mutant and GMR- hid , GMR-GAL4 eye. L 2 exhibits the loss of ventral half of early eye and head involution defective ( hid ) triggers cell-death during later eye development. Surprisingly, newt genes significantly restore missing photoreceptor cells both in L 2 and GMR> hid background by upregulating cell-proliferation and blocking cell-death, regulating evolutionarily conserved Wingless (Wg)/Wnt signaling pathway and exhibit non-cell-autonomous rescues. Further, Wg/Wnt signaling acts downstream of newt genes. Our data highlights that unique newt proteins can regulate conserved pathways to trigger a robust restoration of missing photoreceptor cells in Drosophila eye model with weak restoration capability.

show abstract

Section: Methodsmentioning

confidence: 99%

Newt regeneration genes regulate Wingless signaling to restore patterning in Drosophila eye

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Labeling and visualizing cellular structures and molecules of interest enables quantification of ND hallmarks such as protein localization/aggregation and statistical analysis to evaluate therapeutic value (Rosales-Nieves et al, 2006 ; Daniels et al, 2008 ). Proteins implicated in ND pathology labeled with fluorescent tags aid in studying pathological effects, such as GFP-Aβ42, RFP-Huntingtin, tetracysteine-tagged α synuclein, and tetracysteine-tagged TDP-43 (Roberti et al, 2007 ; Ng et al, 2019 ; Bolus et al, 2020 ; Yeates et al, 2020 ). Immunostaining combined with annotated confocal microscopy can be used to quantify aggregation of specific proteins within whole tissue.…”

Section: The Therapeutic Potential Of Using D Melanogaster ...mentioning

confidence: 99%

Animal Models of Neurodegenerative Disease: Recent Advances in Fly Highlight Innovative Approaches to Drug Discovery

Tello

Williams

Eppler

et al. 2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Neurodegenerative diseases represent a formidable challenge to global health. As advances in other areas of medicine grant healthy living into later decades of life, aging diseases such as Alzheimer's disease (AD) and other neurodegenerative disorders can diminish the quality of these additional years, owed largely to the lack of efficacious treatments and the absence of durable cures. Alzheimer's disease prevalence is predicted to more than double in the next 30 years, affecting nearly 15 million Americans, with AD-associated costs exceeding $1 billion by 2050. Delaying onset of AD and other neurodegenerative diseases is critical to improving the quality of life for patients and reducing the burden of disease on caregivers and healthcare systems. Significant progress has been made to model disease pathogenesis and identify points of therapeutic intervention. While some researchers have contributed to our understanding of the proteins and pathways that drive biological dysfunction in disease using in vitro and in vivo models, others have provided mathematical, biophysical, and computational technologies to identify potential therapeutic compounds using in silico modeling. The most exciting phase of the drug discovery process is now: by applying a target-directed approach that leverages the strengths of multiple techniques and validates lead hits using Drosophila as an animal model of disease, we are on the fast-track to identifying novel therapeutics to restore health to those impacted by neurodegenerative disease.

show abstract

“…All quantitation and analysis were performed with five eye imaginal discs for each genotype analyzed. Statistical analysis was performed using Student's t-test in Microsoft Excel, and graphs were plotted using GraphPad Prism [41][42][43]. Statistical significance in each graph is shown by p-value: ***p < 0.001; **p < 0.01; *p < 0.05.…”

Section: Image Analysismentioning

confidence: 99%

Unbiased Automated Quantitation of ROS Signals in Live Retinal Neurons of Drosophila using Fiji/ImageJ

et al. 2021

Self Cite

View full text Add to dashboard Cite

Numerous imaging modules are utilized to study changes that occur during cellular processes. Besides qualitative (immunohistochemical) or semiquantitative (Western blot) approaches, direct quantitation method(s) for detecting and analyzing signal intensities for disease(s) biomarkers are lacking. Thus, there is a need to develop method(s) to quantitate specific signals and eliminate noise during live tissue imaging. An increase in reactive oxygen species (ROS) such as superoxide (O2•-) radicals results in oxidative damage of biomolecules, which leads to oxidative stress. This can be detected by dihydroethidium staining in live tissue(s), which does not rely on fixation and helps prevent stress on tissues. However, the signal-to-noise ratio is reduced in live tissue staining. We employ the Drosophila eye model of Alzheimer's disease as a proof of concept to quantitate ROS in live tissue by adapting an unbiased method. The method presented here has a potential application for other live tissue fluorescent images.

show abstract

A Two-Clone Approach to Study Signaling Interactions among Neuronal Cells in a Pre-clinical Alzheimer's Disease Model

Cited by 10 publications

References 73 publications

Newt regeneration genes regulate Wingless signaling to restore patterning in Drosophila eye

Newt regeneration genes regulate Wingless signaling to restore patterning in Drosophila eye

Animal Models of Neurodegenerative Disease: Recent Advances in Fly Highlight Innovative Approaches to Drug Discovery

Unbiased Automated Quantitation of ROS Signals in Live Retinal Neurons of Drosophila using Fiji/ImageJ

Contact Info

Product

Resources

About