The research team at the BRIC-Rajiv Gandhi Centre for Biotechnology (BRIC-RGCB), Thiruvananthapuram, has developed a new nanopore-based sensing technology that could help detect biomarkers linked to Parkinson's disease at very low concentrations. The study, led by Dr Mahendran K. R., with contributions from PhD student Varsha Shaji and postdoctoral researcher Dr Neethu Puthumadathil, has been published in Nature Nanotechnology. The technology uses tiny pores made from self-assembling peptides and can identify different forms of disease-associated proteins. Early detection is a major problem in many neurodegenerative diseases because their biomarkers may be present in very small amounts.

The new sensors are designed to overcome this problem by using pores of different sizes, allowing them to examine biomolecules with different shapes and properties. In laboratory testing, the nanopores could distinguish disease-associated and non-disease-associated forms of biomarkers even when they were present in complex mixtures of proteins. The researchers say the technology could eventually help in point-of-care tests that detect disease biomarkers directly from biological fluids such as blood.

What Are Nanopore Sensors?

Nanopores are extremely small hollow structures through which molecules can be detected. In this study, the researchers created pores using short peptides that can naturally assemble into structures with different diameters. The researchers describe these as "self-assembling dual-diameter" nanopores. In simple terms, the same basic system can form smaller and larger pores, giving it flexibility to detect biomolecules of different sizes.

The study found that the pores could detect several types of molecules, including disease-related proteins. One important target was alpha-synuclein, a protein strongly linked to Parkinson's disease. The larger pores could detect different forms of alpha-synuclein, including a disease-associated variant.

How Could This Help Detect Parkinson's Disease?

Parkinson's disease is a progressive neurodegenerative disorder, and finding reliable biomarkers is an important area of research. A biomarker is a measurable biological sign that can provide information about a disease.

One challenge is that potentially useful biomarkers may be present at extremely low levels, making them difficult to detect with conventional techniques. The BRIC-RGCB technology is designed to improve sensitivity by allowing individual biomolecules to interact with the nanopores and produce detectable signals. The researchers also demonstrated that the technology could identify different forms of alpha-synuclein in mixtures containing other proteins. This is important because biological samples such as blood contain many different molecules, which can make it harder to identify a specific disease-related protein.

What Did The Study Find?

The research showed that a single peptide can self-assemble into flexible, alpha-helical nanopores. The researchers engineered the system to produce small and large pores while retaining a common underlying structure. Key findings include:

  • Detection of Parkinson's-related proteins: The larger pores detected multiple forms of alpha-synuclein, including a pathogenic variant associated with Parkinson's disease.
  • Detection at low concentrations: The system was able to identify disease-related biomolecules at very low concentrations.
  • Distinguishing different forms: The sensors could differentiate disease-associated forms from other forms of the same biomarker.
  • Monitoring protein aggregation: The nanopores could track changes in alpha-synuclein as it moved from individual molecules to larger structures called oligomers and fibrils.
  • Potential for other diseases: Smaller pores detected molecules associated with ALS, suggesting that the platform may have applications beyond Parkinson's disease.

Could It Become A Blood Test?

The findings do not mean that a nanopore blood test for Parkinson's disease is currently available. The research represents an experimental sensing platform, and further development and validation would be needed before it could be used routinely in healthcare. However, the researchers say the technology could eventually be adapted for point-of-care devices capable of detecting disease biomarkers directly from biological fluids such as blood. The same approach could potentially be explored for biomarkers associated with other diseases, including cancer.

"Early and accurate detection remains a major challenge in managing neurodegenerative diseases such as Parkinson's and ALS. The nanopore sensor platform demonstrates how advances in nanotechnology and biotechnology can come together to address a critical unmet need in healthcare," said BRIC-RGCB Director Dr Beena Pillai.

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