From Protein Folding to Misfolding: Pathways to Disease and Therapeutic Directions

Proteins are complex macromolecules that perform a variety of biological functions in the living cell only when they are in their native state. Anfinsen’s experiment shows that the native structure of a protein depends on the primary structure of the protein. The native state of protein is attained by protein folding, and this process is initiated by different intra- and intermolecular forces. Thermodynamic stability plays a key role in guiding protein folding, as proteins continuously shift and adjust their structure until they reach their most stable form. Molecular chaperones, cellular enzymes, and other cellular mechanisms drive protein folding. Despite all the guiding factors, proteins may misfold and form toxic aggregates of amyloid fibrils, and it can develop neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington's disease, and prion diseases. Recent studies show that the incidence of neurodegenerative diseases associated with protein folding is becoming a threat to global health. Unfortunately, these diseases are incurable, and therapeutic approaches are currently being researched by scientists to mitigate this issue. Thus, study of protein folding and misfolding remains a key area of research in the bio-medical field.