Small-Molecule Protein-Protein Interaction Inhibitors as Therapeutic Agents for Neurodegenerative Diseases: Recent Progress and Future Directions

摘要

Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common chronic, progressive neurodegenerative diseases affecting an estimated 10% and 1%, respectively, of the elderly population [1,2], with financial costs of hundreds of billions of dollars per year. AD is characterized by the presence of extracellular parenchymal and vascular amyloid deposits containing beta-amyloid peptide (Abeta) and, intracellular neuronal tangles composed of hyperphosphorylated tau. alpha-Synuclein containing Lewy bodies, spherical inclusions found in the cytoplasm of surviving neurons, are the cardinal hallmark of PD. Despite their distinct pathologies, these neurodegenerative diseases are increasingly being realized to have common cellular and molecular mechanisms including protein aggregation and inclusion body formation.