Abstract: Chemical entities are capable of inducing the degradation of the cellular prion protein (PrPC) identified with the pharmacological protein inactivation by folded intermediate targeting (PPI-FIT) methodology.

Abstract: The invention provides compositions and methods for treatment of neurodegenerative diseases or disorders, particularly neurodegenerative diseases and disorders associated with protein aggregation. The present invention is based on the discovery of binding regions on the surface of PrPc, referred to as PrPc Binding Domains (PBD). In particular, the inventors have identified six different binding regions on PrPc, referred to herein as PrP-binding domain-1 (PBD-1), PrP-binding domain-2 (PBD-2), PrP-binding domain-3 (PBD-3), PrP-binding domain-4 (PBD-4), PrP-binding domain-5 (PBD-5), and PrP-binding domain-6 (PBD-6), herein. The PBD-1 to PBD-6 are each defined by a cluster of amino acids located in the globular domain of the protein, e.g., in the C-terminal half of the protein (i.e., in residues 120-230). One embodiment uses residues 127-226.

Abstract: The invention provides compositions and methods for treatment of neurodegenerative diseases or disorders, particularly neurodegenerative diseases and disorders associated with protein aggregation. The present invention is based on the discovery of binding regions on the surface of PrPc, referred to as PrPc Binding Domains (PBD). In particular, the inventors have identified six different binding regions on PrPc, referred to herein as PrP-binding domain-1 (PBD-1), PrP-binding domain-2 (PBD-2), PrP-binding domain-3 (PBD-3), PrP-binding domain-4 (PBD-4), PrP-binding domain-5 (PBD-5), and PrP-binding domain-6 (PBD-6), herein. The PBD-1 to PBD-6 are each defined by a cluster of amino acids located in the globular domain of the protein, e.g., in the C-terminal half of the protein (i.e., in residues 120-230). One embodiment uses residues 127-226.