Therapeutic protein aggregation: mechanisms, design, and control

Mechanisms of protein aggregation.

Aggregation or reversible self-association of protein therapeutics can arise through a number of different mechanisms. Five common aggregation mechanisms are described and their relations to manufacturing processes to suppress and remove aggregates are discussed.

Aging, Protein Aggregation, Chaperones, and Neurodegenerative Disorders: Mechanisms of Coupling and Therapeutic Opportunities

Late onset is a key unifying feature of human neurodegenerative maladies such as Alzheimer's and Parkinson's diseases and prion disorders. While sporadic cases typically emerge during the patient's seventh decade of life or later, mutation-linked, familial cases manifest during the fifth or sixth decade. This common temporal emergence pattern raises the prospect that slowing aging may prevent t...

Mechanisms of protein aggregation and inhibition.

Protein and peptide aggregation raises keen interest due to their involvement in number of pathological conditions ranging from neurodegenerative disorders to systemic amyloidosis. Here, we have reviewed recent advances in mechanisms of aggregation, emerging technologies towards exploration, characterization of aggregate structures, detection at molecular level and the strategies to combat the ...

Conformational stability as a design target to control protein aggregation.

Non-native protein aggregation is a prevalent problem occurring in many biotechnological manufacturing processes and can compromise the biological activity of the target molecule or induce an undesired immune response. Additionally, some non-native aggregation mechanisms lead to amyloid fibril formation, which can be associated with debilitating diseases. For natively folded proteins, partial o...

Inhibition of therapeutic protein aggregation by cyclodextrins