Diseases of protein aggregation and the hunt for potential pharmacological agents.
Protein aggregation is a ubiquitous phenomenon significant to all aspects of science. Notably, the formation of protein aggregates is frequently encountered in biochemical research and biopharmaceutical industry. Formation of protein aggregates is generally regarded to be associated with partially folded intermediate species that are susceptible to self-association due to the exposure of hydrophobic core. Evidence supports the concept that the formation of aggregates in vitro is a generic property of proteins. In human etiology, more than 20 different devastating human diseases have been reported to be associated with protein aggregation. Although protein aggregation diseases have been the center of intense research, much remains to be learned regarding the underlying molecular mechanisms. In this review, the general background information on protein aggregation is first provided. Next, we summarize the properties, characteristics and causes of protein aggregates. Finally, from the perspectives of epidemiology, pathogenesis, existing mechanisms, relevant hypotheses, and current as well as potential therapeutic approaches, two examples of protein aggregation diseases, Alzheimer's disease and cataract, are briefly discussed. Importantly, while a variety of molecules have been suggested, the effective therapeutic drugs for curing the diseases involving protein aggregation have yet to be identified. We believe that a better understanding of the mechanisms of protein aggregation process and an extensive investigation into the drug penetration, efficacy, and side effects will certainly aid in developing the successful pharmacological agents for these diseases.
Wang
Steven S-S
SS
Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan. sswang@ntu.edu.tw
Wu
Josephine W
JW
Yamamoto
Shuichi
S
Liu
Hwai-Shen
HS
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D002386:Cataract / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D011489:Protein Denaturation / Q000187:drug effects*; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
D011506:Proteins