Protein Aggregation

Protein aggregation is the association of multiple protein molecules into larger assemblies. It often occurs when proteins become misfolded or partially unfolded, exposing regions that are normally buried within their native structures. These exposed regions can interact with other protein molecules and promote intermolecular association .^1,2

Protein aggregates can vary greatly in size and structure. Early assemblies may consist of small, soluble groups called oligomers, while larger aggregates can form less ordered deposits or highly organized fibrils. One important type is the amyloid fibril, in which protein molecules form a characteristic ordered structure rich in beta-sheet interactions. Not all protein aggregates are amyloid .^1,2

Cells normally limit inappropriate aggregation through the proteostasis network, which includes molecular chaperones that assist protein folding and systems that remove damaged or misfolded proteins. Aggregation becomes more likely when proteins are prone to misfolding, when environmental conditions destabilize their structures, or when protein quality-control systems cannot adequately manage them .¹

Protein aggregation is related to, but distinct from, protein denaturation. Denaturation describes disruption of a protein's native conformation and can occur without proteins assembling together, whereas aggregation specifically involves association between protein molecules. Although abnormal protein aggregation is associated with several diseases, including amyloid disorders and neurodegenerative diseases, some organized protein aggregates can also have normal biological functions .^1,2