Drug Screening against Neurodegenerative Diseases

Neurodegenerative diseases (NDs) are a group of severely devastating aging-associated disorders characterized by the disruption of cellular proteostasis machinery and sequent forming toxic aggregates in neurons. Due to the demographic increase in the proportion of older individuals in society, NDs have emerged as a major public health challenge, posing a substantial burden on healthcare systems worldwide. Despite decades of intensive research, relatively few current treatments exist for these disorders and offer only symptomatic relief. Therefore, the availability of high-throughput model systems that recapitulate key features of human neurodegenerative diseases is required to dissect the pathological neuronal mechanisms in vivo and amenable to identifying potential compounds for intervention. Given that there are highly conserved neurological pathways between C. elegans and mammals, the simple nematode is extensively used for neuroprotective compound screening. Creative Biogene provides the most common NDs drug screening service based on high-throughput automated drug screening system, involving Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Amyotrophic lateral sclerosis (ALS). With strict and standardized experimental operation and advanced drug screening system, we are dedicated to offering our clients the best service.

C. elegans as a model system against NDs

NDs are a heterogeneous group of aging-associated disorders, presenting different physical manifestations that range from impairment in memory and cognitive processes to progressive interference in motor functions. Common NDs that require particular concerns include AD, PD, HD and ALS. Despite the vast differences in pathogenicity, the NDs are uniquely characterized by a shared hallmark of misfolded protein species, leading to protein aggregation, and thereby termed "proteinopathies". The ND-associated proteins include amyloid-beta (Aβ), TDP-43, tau, α-synuclein (α-syn), huntingtin (Htt), superoxide dismutase (SOD-1), and among others. Despite general knowledge of protein species implicated in NDs, the pathogenesis and causes of NDs are still not well understood and the available neuroprotective treatments are yet to be discovered. Consequently, robust and highly manipulatable model systems are required. Mammalian models are very powerful, whereas are prohibitively expensive and time-consuming for drug screens. The invertebrate organism C. elegans is a simple and attractive model system and presents a complementary approach to mammalian models. To date, a diverse set of C. elegans models of various human NDs have been developed and characterized due to its excellent advantages.

The advantages of C. elegans for NDs study and drug screening

  • The well-characterized and easily accessible nervous system
  • The short generation time (~3 days) and lifespan (~3 weeks)
  • Genetic tractability speeds target identification
  • Neurons with most of the known neurotransmitters in mammalian nervous system
  • Well-characterized synaptic interconnections
  • Visualized neurons with fluorescently labelled in vivo
  • Amenable to high-throughput and high content screening

Service offerings

There are three general methods for producing the C. elegans model, including knocking down the homologue gene of specific human disease in C. elegans, choosing a process in C. elegans that reproduces certain molecular mechanisms of human disease and expressing the human gene in C. elegans to induce a disease-related phenotype. On our platform, we provide the third method combing with microinjecting approaches to generate transgenic worms and further screening potential compounds against NDs. A targeted neuronal expression is implicated in pan-neuronal promoters and specific subtype neuronal promoters, such as dat-1, dopaminergic neurons, mec-7, mechanosensory neurons, and osm-1, chemosensory neurons. Besides, unc-54 and myo-3, the body wall muscle-specific promoters can also be targeted. Particularly, as a traditional method to generate transgenic worms, microinjection is efficient and relatively simple. And our team has accumulated vast experience in expressing specific human genes in C. elegans using microinjection.

C. elegans models of neurodegenerative diseases are generally developed by overexpressing pathogenic proteins in different cells C. elegans models of neurodegenerative diseases are generally developed by overexpressing pathogenic proteins in different cells (Ma L, et al, 2018)

NDs drug screening service in Creative Biogene
Items C. elegans model
Drug Screening Service for Alzheimer's Disease Amyloid-beta (Aβ) models
Drug Screening Service for Parkinson's Disease α-synuclein models
Drug Screening Service for Huntington's Disease Htt-Q150 and Htt513
Drug Screening Service for Amyotrophic Lateral Sclerosis dnc-1 KD model

As a professional C. elegans model service provider, Creative Biogene is dedicated to accelerating our clients' research goals with the most reliable services. If you have any questions about our service, please do not hesitate to contact us for more information.

References

  1. Ma L, et al. (2018). "Caenorhabditis elegans as a model system for target identification and drug screening against neurodegenerative diseases." Eur J Pharmacol. 819:169-180.
  2. Van Pelt, K. M., et al. (2020). "Caenorhabditis elegans as a model system for studying aging-associated neurodegenerative diseases". Translational Medicine of Aging.

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