• To explore how plants deal with toxic protein aggregation, Dr. Ernesto Llamas, first author of the study, and colleagues introduced the toxic mutant protein huntingtin in plants, which causes cell death in human neurons. (phys.org)
  • HTT exon 1 with expanded polyQ was fused with either N-terminal or C-terminal fragments of Venus fluorescence protein and expressed in pharyngeal muscles and associated neurons, respectively, of C. elegans . (en-journal.org)
  • Development and further characterization of a small subclass of rat olfactory receptor neurons that shows immunoreactivity for the HSP70 heat shock protein. (morimotolab.org)
  • There are several major differences that distinguish C. elegans neurons from their mammalian counterparts. (biomedcentral.com)
  • First, C. elegans neurons are small (5-10 μm of their soma size), and most of them do not have accompanying glial cells [ 10 ]. (biomedcentral.com)
  • Sensory neurons of the amphid and phasmid, which are C. elegans sensory organs in the head and in the tail, respectively, are associated with glial cells but do not have myelination around their processes [ 10 ]. (biomedcentral.com)
  • Reviewer #1: The human microbiome is suspected of influencing morbidity and mortality due to protein conformational diseases such as Alzheimer's, Parkinson's and Lou Gehrig's diseases. (plos.org)
  • Recent advances suggest that an age-related decline in proteostasis capacity allows the manifestation of various protein-aggregation diseases, including Alzheimer's disease and Parkinson's disease. (nature.com)
  • Protein misfolding and aggregation are common pathological features of several human diseases, including Alzheimer's disease and type 2 diabetes. (nature.com)
  • AIP-1 ameliorates beta-amyloid peptide toxicity in a Caenorhabditis elegans Alzheimer's disease model. (neurotree.org)
  • In the case of protein misfolding diseases, a wide range of model systems have been developed to investigate different aspects of disorders including Huntington's disease, Parkinson's disease, Alzheimer's disease as well as amyotrophic lateral sclerosis. (scienceopen.com)
  • Recent studies have investigated the role of molecular chaperones in amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease and polyglutamine diseases. (scienceopen.com)
  • The pathological signature in numerous neurodegenerative diseases are characterized by the accumulation of intracellular or extracellular protein aggregates composed of amyloid fibrils [ 1 ], such as senile plaques and neurofibrillary tangle composed of β-amyloid, microtubule associated protein tau in Alzheimer's disease (AD), and Lewy bodies composed of α-synuclein in Parkinson's disease (PD). (biomedcentral.com)
  • To address this, we examined the role of natural variation in defining the susceptibility of genetically diverse individuals to protein aggregation and toxicity, using the Caenorhabditis elegans polyglutamine model. (biomedcentral.com)
  • Suppression of in vivo beta-amyloid peptide toxicity by overexpression of the HSP-16.2 small chaperone protein. (neurotree.org)
  • In a genomewide screen, the largest class of toxicity modifiers were proteins functioning at this same step, including the Rab guanosine triphosphatase Ypt1p, which associated with cytoplasmic alphaSyn inclusions. (scienceopen.com)
  • Due to the central role of autophagy in the removal of aggregation-prone proteins, a better understanding of mechanisms controlling autophagy is essential for the identification of novel therapeutic opportunities for multiple disease states. (elifesciences.org)
  • This prompted us to investigate if mir-1 is required for preventing the accumulation of aggregation-prone proteins. (elifesciences.org)
  • Conversion of green fluorescent protein into a toxic, aggregation-prone protein by C-terminal addition of a short peptide. (neurotree.org)
  • Molecular chaperones provide a first line of defence against misfolded, aggregation-prone proteins and are among the most potent suppressors of neurodegeneration known for animal models of human disease. (scienceopen.com)
  • Modeling microbiome connections to organismal protein homeostasis (proteostasis) has been successful in the nematode C. elegans, where ingestion of human pathogenic bacteria has been demonstrated to cause proteostatic collapse. (plos.org)
  • Because protein molecules are highly dynamic, constant chaperone surveillance is required to ensure protein homeostasis (proteostasis). (nature.com)
  • Figure 6: Protein fates in the proteostasis network. (nature.com)
  • Loss of glutathione redox homeostasis impairs proteostasis by inhibiting autophagy-dependent protein degradation. (neurotree.org)
  • We outline a protocol to quantifiably measure proteostasis in two different Caenorhabditis elegans tissues through heterologous expression of polyglutamine repeats fused to a fluorescent reporter. (jove.com)
  • Jerome Goudeau team published a paper entitled "Addendum: A lysosomal switch triggers proteostasis renewal in the immortal C. elegans germ lineage" using our strain PHX798 gld-1(syb798) . (sunybiotech.com)
  • In their publication "In-planta expression of human polyQ-expanded huntingtin fragment reveals mechanisms to prevent disease-related protein aggregation" in Nature Aging , they showed that a synthetic enzyme derived from plants -stromal processing peptidase (SPP)-reduces the clumping of proteins responsible for the pathological changes in models of Huntington's disease in human cells and the nematode Caenorhabditis elegans. (phys.org)
  • Producing the plant SPP in models of Huntington's disease such as human cultured cells and worms like the nematode C. elegans reduced protein clumps and symptoms of disease. (phys.org)
  • The powerful genetics, simple anatomy and short life span of the nematode Caenorhabditis elegans offer unique advantages in unraveling the molecular genetic network that regulates the integrity of neuronal structures and functions during aging. (biomedcentral.com)
  • Huntingtin contains a few domains that suggest particular functions, including WW domains and caspase cleavage sites ( 7 , 8 ), but the function of the protein remains unknown. (jci.org)
  • Western blot analysis of HD brain tissue shows full-length huntingtin protein in the nuclear fraction as well as abundant immunopositive bands at lower molecular weight, suggesting proteolytic products in the nucleus. (jci.org)
  • Huntingtin-interacting protein 1-related protein is a protein that in humans is encoded by the HIP1R gene. (wikipedia.org)
  • Huntingtin (Htt) is a multi-function protein of the brain. (benthamscience.com)
  • Huntington's disease is a genetic neurological disorder caused by a repeated expansion of the CAG trinucleotide, causing instability in the N-terminal of the gene coding for the Huntingtin protein. (benthamscience.com)
  • The mutation leads to the abnormal expansion of the production of the polyglutamine tract (polyQ) resulting in the form of an unstable Huntingtin protein commonly referred to as mutant Huntingtin. (benthamscience.com)
  • In contrast to animal and human models, they found that Arabidopsis thaliana plants actively removed huntingtin protein clumps and avoid harmful effects. (phys.org)
  • We were pleased to observe that expression of the plant SPP protein improved motility of C. elegans worms affected by huntingtin even at later aging stages where the symptoms are even worse," said Dr. Hyun Ju Lee, a postdoc also involved in the study. (phys.org)
  • For example in HD, the age of neurological onset is strongly associated with the length of polyglutamine (polyQ) expansion in huntingtin protein. (biomedcentral.com)
  • Huntington disease (HD) is an inherited neurodegenerative disorder characterized by motor and cognitive dysfunction caused by expansion of polyglutamine (polyQ) repeat in exon 1 of huntingtin (HTT). (en-journal.org)
  • Sedimentation Velocity Analysis With Fluorescence Detection of Mutant Huntingtin Exon 1 Aggregation in Drosophila Melanogaster and Caenorhabditis Elegans. (neurotree.org)
  • Huntington's disease is among the so called polyglutamine (polyQ) diseases, a group of neurodegenerative disorders caused by multiple repetitions of glutamine amino acids in specific proteins. (phys.org)
  • An excessive number of polyQ repeats can cause proteins to aggregate or accumulate in harmful and damaging protein deposits, leading to cellular dysfunction and death. (phys.org)
  • They express hundreds of proteins containing polyQ repeats, but no pathologies from these factors have been reported. (phys.org)
  • Expansion of polyQ increases the propensity for HTT protein aggregation, process known to be implicated in neurodegeneration. (en-journal.org)
  • Transmission of polyQ proteins was detected using bimolecular fluorescence complementation (BiFC). (en-journal.org)
  • The C. elegans model presented here would be a useful in vivo model system for the study of polyQ aggregate propagation and might be applied to the screening of genetic and chemical modifiers of the propagation. (en-journal.org)
  • Extension of polyQ causes aggregation of HTT protein. (en-journal.org)
  • We found that the conserved PTEN-induced putative kinase (PINK1/PINK-1) and the E3 ubiquitin-protein ligase parkin (PDR-1), which are required for mitochondrial autophagy (mitophagy), underlie stereotyped differences in heteroplasmy of a deleterious mitochondrial genome mutation (ΔmtDNA) between major somatic tissues types in Caenorhabditis elegans . (biorxiv.org)
  • Heteroplasmy differences between tissues have also been observed in C. elegans . (biorxiv.org)
  • In this system, large combinatorial libraries of macrocyclic molecules are biosynthesized in Escherichia coli cells and simultaneously screened for their ability to rescue pathogenic protein misfolding and aggregation using a flow cytometric assay. (nature.com)
  • A detailed understanding of the molecular basis of chaperone-mediated protection against neurodegeneration might lead to the development of therapies for neurodegenerative disorders that are associated with protein misfolding and aggregation. (scienceopen.com)
  • Here, we report that the microRNA miR-1 regulates the autophagy pathway through conserved targeting of the orthologous T re-2/ B ub2/ C DC16 (TBC) Rab GTPase-activating proteins TBC-7 and TBC1D15 in Caenorhabditis elegans and mammalian cells, respectively. (elifesciences.org)
  • The mammalian sirtuin (SIRT) family, evolutionally conserved proteins belonging to class III histone deacetylases (HDACs), comprises seven members. (biomedcentral.com)
  • The mammalian genome comprises nuclear DNA (nDNA) derived from both parents and mitochondrial DNA (mtDNA) that is maternally inherited and encodes essential proteins required for oxidative phosphorylation. (regenerativemedicine.net)
  • The abnormal aggregation and accumulation of specific proteins in the form of cytoplasmic inclusion is common pathological feature of most age-related neurodegenerative diseases, such as Alzheimer disease (AD), Parkinson disease (PD), Huntington disease (HD) and amyotrophic lateral sclerosis (ALS). (en-journal.org)
  • We propose that molecular chaperones are neuroprotective because of their ability to modulate the earliest aberrant protein interactions that trigger pathogenic cascades. (scienceopen.com)
  • Defective autophagy results in accumulation of toxic protein aggregates that detrimentally affect cellular function and organismal survival. (elifesciences.org)
  • Llamas said, "Unlike humans, plants have chloroplasts, an extra cellular type of organelle that could provide an expanded molecular machinery to get rid of toxic protein aggregates. (phys.org)
  • Unlike humans who suffer from proteinopathies caused by the toxic aggregation or cluster of proteins, plants do not experience these kinds of diseases. (phys.org)
  • Their hope is that the use of plant proteins could lead to new therapeutic approaches for treating Huntington's disease and other neurodegenerative diseases. (phys.org)
  • Monogenic gain-of-function protein aggregation diseases, including Huntington's disease, exhibit substantial variability in age of onset, penetrance, and clinical symptoms, even between individuals with similar or identical mutations. (biomedcentral.com)
  • Resistance to protein aggregation and the ability to restrict its associated cellular dysfunction are independently controlled by the natural variation in genetic background, revealing important new considerations in the search for targets for therapeutic intervention in conformational diseases. (biomedcentral.com)
  • nine of these diseases, referred to as polyglutamine diseases, are associated with. (biomedcentral.com)
  • Quantifying Tissue-Specific Proteostatic Decline in Caenorhabditis elegans Maria I. Lazaro-Pena 1 , Adam B. Cornwell 1 , Andrew V. Samuelson 1 1 Department of Biomedical Genetics, University of Rochester Medical Center Proteostatic decline is a hallmark of aging, facilitating the onset of neurodegenerative diseases. (jove.com)
  • Deposition of the pathological signature proteins in the brain is the hallmark in various kinds of neurodegenerative diseases. (biomedcentral.com)
  • Interaction of intracellular beta amyloid peptide with chaperone proteins. (neurotree.org)
  • Many neurodegenerative disorders are characterized by conformational changes in proteins that result in misfolding, aggregation and intra- or extra-neuronal accumulation of amyloid fibrils. (scienceopen.com)
  • Fusion of autophagosomes with lysosomes results in degradation of their contents and thereby removes toxic proteins and damaged organelles from cells to maintain homeostasis. (elifesciences.org)
  • On the origin of BAG(3) and its consequences for an expansion of BAG3's role in protein homeostasis. (unimedizin-mainz.de)
  • Appropriate regulation of autophagy is crucial for clearing toxic proteins from cells. (elifesciences.org)
  • Autophagy is a degradation system that involves sequestration of cytoplasmic proteins and organelles by double-layered membranes that form vesicles called autophagosomes. (elifesciences.org)
  • 2023). Identification of potential selective autophagy receptors from protein-content profiling of autophagosomes. (unimedizin-mainz.de)
  • Yet age of onset can vary by several decades in people carrying the same length polyglutamine expansion, and a large proportion of this residual variation is genetic in nature and may be due to polymorphisms in other genes [ 12 - 15 ]. (biomedcentral.com)
  • By purifying and analysing mitochondria from different cell types, we show that PINK-1 and PDR-1 are required to set heteroplasmy differences between major somatic tissue groups in C. elegans and that removal of these genes equalises ΔmtDNA heteroplasmy across the organism. (biorxiv.org)
  • The multifunctional regulator nuclear factor erythroid 2-related factor (Nrf2) is considered not only as a cytoprotective factor regulating the expression of genes coding for anti-oxidant, anti-inflammatory and detoxifying proteins, but it is also a powerful modulator of species longevity. (springer.com)
  • The major characteristics of Nrf2 are to some extent mimicked by Nrf2-dependent genes and their proteins including heme oxygenase-1 (HO-1), which besides removing toxic heme, produces biliverdin, iron ions and carbon monoxide. (springer.com)
  • In spite of these differences in life span, however, genes or signaling pathways that influence aging of C. elegans or the replicative span of Saccharomyces cerevisiae (baker's yeast) have been shown to be critical for longevity control in fly and in mice [ 1 , 2 ]. (biomedcentral.com)
  • This involves silencing genes, blocking their production of RNA and protein. (doctorsaredangerous.com)
  • 2015). Dominant negative effect of polyglutamine expansion perturbs normal function of ataxin-3 in neuronal cells . (up.pt)
  • In this review, we first summarize recent breakthroughs in the morphological and functional characterization of C. elegans neuronal aging. (biomedcentral.com)
  • As a robust genetic model for aging, insights from C. elegans neuronal aging studies will contribute to our mechanistic understanding of human brain aging. (biomedcentral.com)
  • Founded in 2016, SunyBiotech Co., Ltd is committed to providing high-quality and efficient C. elegans gene editing services to p restigious university laboratories worldwide. (sunybiotech.com)
  • Since May 2017, SunyBiotech has undertaken C. elegans gene editing services. (sunybiotech.com)
  • Hartl, F. U. Molecular chaperones in cellular protein folding. (nature.com)
  • Molecular Chaperone Machines: Chaperone Activities of the Cyclophilin Cyp-40 and the Steroid Aporeceptor-Associated Protein P23. (morimotolab.org)
  • Utility of these systems broadly correlates with evolutionary complexity: small animal models such as rodents and the fruit fly are appropriate for pharmacological modeling and cognitive/behavioral assessment, the roundworm Caenorhabditis elegans allows analysis of tissue-specific disease features, and unicellular organisms such as the yeast Saccharomyces cerevisiae and the bacterium Escherichia coli are ideal for molecular studies. (scienceopen.com)
  • 2007). Functional genomics and biochemical characterization of the C. elegans orthologue of the Machado-Joseph disease protein ataxin-3 . (up.pt)
  • They house their own genome (mtDNA), as well as RNA and protein-synthesizing systems, which together code and coordinate the assembly of core subunits of oxidative phosphorylation (OXPHOS). (biorxiv.org)
  • Oxidative stress generated during such stressful conditions may damage DNA and proteins, and as a consequence the cellular processes are disturbed. (springer.com)
  • Furthermore, GSOs protected cells against GLU-induced apoptosis by reducing the expression of the mitochondrial apoptosis-associated Bcl-2 family effector proteins and protected cells from GLU-induced oxidative damage by increasing the nuclear translocation of Nrf2 and HO-1 expression. (sdbonline.org)
  • Körschgen H, Baeken M, Schmitt D, Nagel H, Behl C . Co-chaperone BAG3 enters autophagic pathway via its interaction with microtubule associated protein 1 light chain 3 beta. (unimedizin-mainz.de)
  • We were surprised to see plants completely healthy, even though they were genetically producing the toxic human protein. (phys.org)
  • Indeed, the scientists discovered that the chloroplasts, the plant-specific organelles that perform photosynthesis, were the reason why plants do not show toxic protein deposits. (phys.org)
  • But in the cellular environment, newly synthesized proteins are at great risk of aberrant folding and aggregation, potentially forming toxic species. (nature.com)
  • After several years of accumulation, SunyBiotech has become a well-known brand recognized by the academic field of C.elegans . (sunybiotech.com)
  • Thus, our C. elegans model can serve as a powerful tool to dissect the contribution of natural variation to individual susceptibility to proteotoxicity. (biomedcentral.com)
  • We believe that in the future, "SunyBiotech C.elegans " will provide a good experiment model for more researchers, reveal more scientific secrets hidden in C. elegans , and make greater contributions to the cause of life science. (sunybiotech.com)
  • In this chapter, we highlight key advances in our understanding of protein misfolding/unfolding disease provided by model systems. (scienceopen.com)
  • Here, we exploited mutation correction of iPS cells and conserved proteotoxic mechanisms from yeast to humans to discover and reverse phenotypic responses to α-synuclein (αsyn), a key protein involved in Parkinson's disease (PD). (scienceopen.com)
  • Nrf2 consists of six functional Neh domains (Neh1-Neh6), from which, the amino-terminal Neh2 domain controls binding Keap1-the inhibitor protein Kelch-like ECH-associated protein 1, that is responsible for the cytosolic sequestration of Nrf2 under physiological conditions (Fig. 2 a). (springer.com)
  • Therefore, this work provides a potential therapeutic strategy for protein aggregation disorders. (elifesciences.org)
  • Most proteins must fold into defined three-dimensional structures to gain functional activity. (nature.com)
  • Kokona B, Smith ZP, Fairman R, Laue T , Link C , Roberts C. Sedimentation Velocity Analysis of Polyglutamine Assembly in C. elegans using a Fluorescence Detection System Biophysical Journal . (neurotree.org)
  • Skach, W. R. Cellular mechanisms of membrane protein folding. (nature.com)
  • The multidisciplinary team identified the chloroplast plant protein SPP as the reason why plants are unaffected by the problematic human protein. (phys.org)
  • Bartlett, A. I. & Radford, S. E. An expanding arsenal of experimental methods yields an explosion of insights into protein folding mechanisms. (nature.com)
  • Small interfering RNAs induce macrophage migration inhibitory factor production and proliferation in breast cancer cells via a double-stranded RNA-dependent protein kinase-dependent mechanism. (wikidata.org)