Drug Screening Service for Alzheimer's Disease

The most common cause of dementia is Alzheimer's disease (AD), a progressive neurodegenerative disorder that manifests cognitive impairment, progressive memory loss and neurodegeneration. AD is closely related to age, characterized by the prevalence of extracellular Aβ plaques and intracellular neurofibrillary tangles. The two distinct types of inclusions are derived from the proteolysis of the amyloid precursor protein (APP) and the hyperphosphorylation of the microtubule-associated protein tau, respectively. Due to the disease manifests on several scales, including molecular, cellular and organismal, it is difficult within the organismal phenotype to replicate and exploit for screening in vitro. Despite years of extensive research, the underlying pathological molecular mechanisms of AD remain unclear. Caenorhabditis elegans is a model organism advantageous for studying AD. Here, we present a high-throughput screening platform using the powerful model system C. elegans to study AD.

Caenorhabditis elegans: an ideal organism for modeling age-related AD

The study of AD pathophysiology requires mammalian models, and the invertebrate organism C. elegans can be a valuable model. Apart from the complex biochemical pathways conserved with their mammalian counterparts, there are AD-related genes present in the worm mutations, including apl-1 (an APP-related gene), ptl-1 (a tau homolog), sel-12 and hop-1 (presenilin homologs). The conserved characteristics, defined neuroanatomy and the short lifespan of the worm are unique superiorities for probing neurotoxic factors. Given that the distinctive features and tractability of C. elegans, the neuronal connectivity in the nematodes has already been established. Therefore, it is also advantageous in modeling learning and memory impairments seen during AD.

The development of a C. elegans model for AD usually requires the insertion of genes that trigger the worm's genome to express the toxic proteins shown to recapitulate AD pathologies, including TDP-43, tau, amyloid-beta, and alpha-synuclein. The C. elegans has been successfully employed to establish the model of AD, developing delayed swallowing, paralysis and other 'phenotypes' of disease.

Service offerings

  • the transgenic AD model strain (GRU102)

On our platform, the transgenic AD model strain (GRU102) that constitutively expresses a pathogenic human amyloid-beta peptide (Aβ1-42) is applied for high-throughput screening of potential compounds against AD. The strain is a novel transgenic C. elegans AD model that recapitulates key aspects of mitochondrial toxicity observed in human AD. The toxic effects of Aβ1-42 in C. elegans show progressive neuromuscular deficits and shortened lifespan. As for the phenotypes, GRU102 exhibits mild and slow-progressing when compared to other strains, which is reminiscent of human AD.

  • Automated workflow

In order to fully leverage the advantages of the model and provide a better service experience for customers, we use a protocol that involves scalable phenotypic assay implemented on automated systems. The protocol is based on a phenotype and assay related to Aβ-induced neuromuscular failure in GRU102. Here we adopt the swim exhaustion phenotype to distinguish Aβ-overexpressing animals from control before lifespan detriment or metabolic deficit are robustly detectable. In addition, to facilitate scaling, standard fluid handling and automation technologies are also employed. The quantifiable phenotype is performed with observations in fewer than 15 animals per condition.

Workflow of compounds screening for AD

Workflow of compounds screening against AD

Creative Biogene is a dedicated provider of C. elegans model services. Since the nematode system has been successfully employed to establish the model of AD and demonstrated its value in screening potential compounds of human neurodegenerative disorders. Here we offer one-stop service covering steps from strain cultivation to data analysis. When you choose Creative Biogene, you will find your best and most reliable partner. Please feel free to contact us for more details of our service. We are looking forward to cooperating with you!

Reference

  1. Teo E, et al. (2020). "A high throughput drug screening paradigm using transgenic Caenorhabditis elegans model of Alzheimer's disease[J]." Translational Medicine of Aging. 4: 11-21.

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