α-Synuclein Degrader Compound Screen Assay

Neurological diseases cause huge social losses and heavy annual economic burdens, so it is urgent to develop new drugs. Equipped with world-leading technology platforms and professional scientific staff, Creative Biolabs provides the novel α-Synuclein degrader compound screen assay for our clients all over the world.

Introduction of α-Synuclein

Encoded by the SNCA gene, Alpha-synuclein is a neuronal protein that is abundant in the brain and less abundant in the heart, muscle, and other tissues. Human alpha-synuclein consists of 140 amino acids. First detected in an amyloid-enriched fraction, alpha-synuclein fragment, also known as the non-Abeta component (NAC) of Alzheimer's disease amyloid, has been proved to be the fragment of its precursor protein, NACP. In the brain, alpha-synuclein can be detected in the axon terminals of presynaptic neurons and interacts with phospholipids and proteins.

Parkinson's disease (PD) is the second most common neurodegenerative disease that causes unintended or uncontrollable movements. Studies have shown that α-synuclein is the major component of Lewy bodies in patients with PD. Experiments in transgenic mice and transgenic flies showed that overexpression of α-syn may lead to progressive motor deficits, and reducing α-syn accumulation may be a therapeutic strategy for treating PD. In this case, screening of the α-Synuclein degrader compound presents great potential for drug development against PD.

Fig. 1 CRISPR-Cas9 whole genome-wide screening identified several proteasome subunit genes required for canthin-6-one-induced α-syn degradation.^1,2

α-Synuclein Degrader Compound Screening

Now Creative Biolabs provides the novel α-synuclein degrader compound screen assay for our clients. We have developed a tetracycline-inducible expression system to simultaneously induce the expression of α-syn-EGFP and mCherry for the screening of potential compounds that degrade α-syn. For example, canthin-6-one is an α-syn lowering compound to promote α-syn degradation. In addition, canthin-6-one can also upregulate PSMD1 and enhance UPS function by activating PKA. Using CRISPR/Cas9 genome-wide screening technology, RPN2/PSMD1, the 26S proteasome non-ATPase regulatory subunit 1, has been identified as a target gene for the pharmacological activity of canthin-6-one. In our completed projects, endogenous α-Synuclein (α-Syn) evaluation has been validated. Batches of a-Syn degrader compounds have been obtained using this validated assay. What's more, we performed parallel cytotoxicity assessments by CTG. In summary, you can obtain many valuable compounds using our screening technology.

Equipped with world-leading technology platforms and professional scientific staff, Creative Biolabs is willing to provide the α-Synuclein degrader compound screen assay for our clients. If you are interested in our services, please do not hesitate to contact us for more details.

References

1. Yuan, Ning-Ning, et al. "Canthin-6-one accelerates alpha-synuclein degradation by enhancing UPS activity: drug target identification by CRISPR-Cas9 whole genome-wide screening technology." Frontiers in Pharmacology 10 (2019): 16.
2. used under Open Access license CC BY 4.0,without modification.