Abstract
Prion diseases, also known as transmissible spongiform encephalopathies, are caused by the accumulation of abnormal isoforms of the prion protein (scrapie isoform of the prion protein, PrPSc) in the central nervous system. Many compounds with anti-prion activities have been found using in silico screening, in vitro models, persistently prion-infected cell models, and prion-infected rodent models. Some of these compounds include several types of polymers. Although the inhibition or removal of PrPSc production is the main target of therapy, the unique features of prions, namely protein aggregation and assembly accompanied by steric structural transformation, may require different strategies for the development of anti-prion drugs than those for conventional therapeutics targeting enzyme inhibition, agonist ligands, or modulation of signaling. In this paper, we first overview the history of the application of polymers to prion disease research. Next, we describe the characteristics of each type of polymer with anti-prion activity. Finally, we discuss the common features of these polymers. Although drug delivery of these polymers to the brain is a challenge, they are useful not only as leads for therapeutic drugs but also as tools to explore the structure of PrPSc and are indispensable for prion disease research.
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We thank all the collaborators, researchers and technicians involved in our research described in this review for their contributions.
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This review was supported by grants from the Japan Society for the Promotion of Science (19K22479 and 19H03570) and the Alberta Prion Research Institute Program (201700012).
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Teruya, K., Doh-ura, K. Therapeutic development of polymers for prion disease. Cell Tissue Res 392, 349–365 (2023). https://doi.org/10.1007/s00441-022-03604-1
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DOI: https://doi.org/10.1007/s00441-022-03604-1