C9orf72 Di-peptide Aggregation Assay Service

The aggregation of C9orf72-related dipeptide repeat proteins (DPRs) is a central pathogenic event in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Critically, this process is both highly heterogeneous and interventionable. Our advanced testing services offer a powerful platform for dissecting DPR toxicity, identifying effective therapeutic strategies, and validating crucial biomarkers. For further information regarding the products and services provided, project-specific consultation, and pricing, please submit an inquiry here.

C9orf72 Di-peptide Aggregation in ALS

The hexanucleotide repeat expansion (GGGGCC) within the C9orf72 gene represents the most prevalent genetic cause of FTLD and ALS. A central pathological hallmark is the generation of DPRs, including poly-glycine-alanine (poly-GA), poly-glycine-proline (poly-GP), and poly-glycine-arginine (poly-GR), through repeat-associated non-ATG (RAN) translation. These DPRs abnormally aggregate within neurons, forming characteristic inclusion bodies. Research confirms that DPR aggregation not only directly induces mitochondrial dysfunction and nucleocytoplasmic transport abnormalities but is also closely linked to TDP-43 pathology, a hallmark of 90% of ALS cases. Consequently, precise detection of DPR aggregation dynamics is crucial for elucidating disease mechanisms and developing effective therapies.

C9orf72 Di-peptide Aggregation Assays at Creative Biolabs

• Complete Coverage of DPR Protein Variants

Utilizing highly specific antibodies, our services support the detection of all DPR subtypes, including poly-GA, poly-GR, and poly-PR, compatible with Western blotting (WB), immunohistochemistry (IHC), and cell imaging analysis. Our services differentiate the aggregation patterns of distinct DPRs; for example, poly-GA primarily forms cytoplasmic inclusions, whereas poly-GR and poly-PR tend to induce nuclear aggregation.

Fig.1 The aggregation of PR12 and GR12 was initiated by a short period of agitation, and the samples were analyzed as a function of time by dot blot analysis.^{2, 3}

• Real-Time Analysis of Aggregation and Toxicity Pathways

Our services feature diverse, inducible cell models designed to replicate C9orf72 mutations, enabling the dynamic monitoring of aggregation and toxicity mechanisms. We facilitate investigations into the length-dependent neurotoxicity of DPRs, demonstrating that longer DPRs exhibit increased toxicity. Furthermore, we provide comprehensive assessments of DPR-mediated disruptions to critical cellular processes, including mitochondrial function, autophagy pathways, and nucleocytoplasmic transport.

• Tailored Research Solutions

As our understanding of C9orf72 DPRs advances, we are committed to pioneering novel detection methodologies and technologies to enhance the diagnosis and treatment of neurodegenerative disorders. Recognizing the unique requirements of each research project, we offer fully customized experimental design and data analysis support, ensuring optimal results for our clients.

Contact us today to design a personalized C9orf72 DPR research strategy and accelerate the discovery of innovative therapeutic targets for neurodegenerative diseases.

References

1. Schmitz, Alexander, et al. "Emerging perspectives on dipeptide repeat proteins in C9ORF72 ALS/FTD." Frontiers in cellular neuroscience 15 (2021): 637548.
2. Bhatt, Nemil, et al. "C9orf72-associated dipeptide protein repeats form A11-positive oligomers in amyotrophic lateral sclerosis and frontotemporal dementia." Journal of Biological Chemistry 300.2 (2024): 105628.
3. Distributed under Open Access license CC BY 4.0, without modification.