Small molecules inducing cellular prion protein degradation

This invention concerns the field of medicine and focuses in particular on new solutions for treating disorders related to cellular prion protein (PrPC), a protein involved in several neurodegenerative diseases. .

How does it work?

As we age, an error can occur in the way proteins fold, taking on abnormal forms rich in structures called β-sheets; these forms can aggregate into amyloid fibrils that interfere with the functioning of neurons and are involved in the development of several neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, ALS, and prion diseases. Prion diseases, or transmissible spongiform encephalopathies, are caused by the transformation of normal prion protein (PrPC) into an abnormal, misfolded form (PrPSc) that accumulates in the central nervous system.

The present technology enables the use of a new method to develop drugs, called PPI-FIT, which makes it possible to identify small molecules capable of binding to a temporary and unstable form of the prion protein PrPC, favouring its degradation before it becomes functional. This approach reduces PrPC levels in cells and holds promise for the treatment of several PrPC-related conditions, including neurodegenerative diseases (such as Alzheimer’s, Parkinson’s, and prion diseases), neuroinflammatory disorders (such as multiple sclerosis), and some cancers, including glioblastoma and stomach, breast, and colon cancers.

Applications

• Treatment of neurodegenerative diseases;
• Treatment of neuroinflammatory disorders;
• Therapeutic interventions for other misfolded proteins.

Advantages

• Targeting of temporary forms of the protein;
• Increased selective degradation;
• Reduction of side effects;
• Versatility.