Protein aggregation: current scenario and recent developments

2012-05-16Aggregation of proteins is the major topic of discussion and debate in the biopharmaceutical industry. Various chemical and physical properties of proteins have been studied and manipulated in order to overcome this major hurdle during biopharmaceutical product formulation. Huge investments are done in order to understand the mechanisms underlying abnormal protein aggregation during the production process as well as in-vivo. Theories explaining this aggregation process are manipulated in the industry in order to attain the protein drug in its highest quality. Further, based on the nature and extent of such aggregates formed it is possible to classify the different types of aggregates. As aggregation is assumed to be an end-product of undesirable events occurring through the molecular cascade, based on such classification one can try to reach to the possible causative factor in the molecular cascade that leads to aggregation. Various detection techniques have been utilized to check the presence of aggregate formation while the protein drug is in its initial processing steps. Such techniques provide a lot of information on physical characteristics and real time detection on how the process of aggregation moves in its pathway. Further, we have discussed the most widely used techniques and strategies to inhibit aggregation at the in-vitro level. Storage of proteins in order to maintain it viable for a sufficiently long interval of time is very important. Techniques on effective storage and environmental conditions that may affect as a causative parameter in initiation of aggregation have been discussed. Taking a step further in this direction, many neurodegenerative disorders have found their origins in the formation of protein aggregates, called amyloids. We have discussed two major neurodegenerative diseases: Alzheimer’s disease and Prion Disease and their pathogenesis