One of the causes for neurodegenerative diseases including Alzheimer s disease, Parkinson s disease and prion diseases is protein misfolding and aggregation. Drugs designed to inhibit or reverse the conformational changes may thus be a valid therapy for protein conformational diseases. However, the effective pharmacological tools for these diseases are not yet available. Here we discuss therapeutic approaches to prion diseases and other neurodegenerative diseases from the biological evaluation of four new libraries of the compounds designed and synthesized on nanotechnology, computational study and chemistry. We also studied their mechanism of action in inhibiting prion replication. The most active anti-prion compounds may be therapeutic agents for the diseases.