Protein Folding and Misfolding: Deciphering Mechanisms of Age-Related Diseases

Abstract

Proteins are essential molecules in all organisms and involved in most biological processes. Therefore, the correct folding of proteins into their native structure is the prerequisite for a functional living system. Most small proteins fold spontaneously into their native functional state in a test tube without any assistance. The folding of proteins in a cellular context is, however, more complex and usually requires molecular chaperones, assistants of protein folding. Molecular chaperones ensure that proteins reach their native state, prevent protein misfolding and eventually refold misfolded proteins. If the molecular chaperones and other protein quality control (PQC) systems such as the ubiquitin-proteasome system (UPS) or autophagy fail, protein misfolding occurs, often followed by the formation of aggregates including amyloid fibrils. Many diseases are known to be associated with protein misfolding and aggregation and they can be termed as protein-folding diseases, proteinopathies or proteopathies. In this chapter, we describe some of the essential biological processes, which determine protein folding, misfolding and aggregation and discuss prominent age-related proteinopathies, including neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease.