Abstract
Unraveling the characteristics and putative applications of naturally occurring protein aggregates has received an increasing interest during the last years. For example, the finding that the proteins embedded within bacterial inclusion bodies are, at least partially, biologically functional opened new opportunities for their rational design and application as naturally self-immobilized biocatalysts or as new drug delivery systems (“nanopills”). In another scenario, it is well established that “conformational diseases” are caused by misfolding and protein aggregation in different cells and tissues. The presence of such protein aggregates is a hallmark of these conditions, therefore becoming an excellent target for new therapeutic approaches for such devastating pathologies. Aggresomes are protein aggregates found in eukaryotic cells when the intracellular protein degradation machinery is overtitered. These protein-based nanoparticles are increasingly becoming excellent models in studies aimed to obtain a better understanding and control over protein aggregation processes in eukaryotic cells. In this work, we focus on some of the latest findings in the field of putative aggresome applications in biotechnology, as a new type of self-assembled immobilized biocatalysts, and in nanomedicine, mainly on their relationship with conformational diseases and the rational design of better therapeutics through a deeper understanding of protein aggregation processes.
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Acknowledgments
The author acknowledges the financial support received for funding our research on protein-based nanotherapeutics and biomaterials from Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR, 2014SGR-132), FIS (PS09-00165 and PI12/00327), Fundació La Marató de TV3 (TV32009-101235, TV32013-132031, and TV32013-133930), INIA (RTA2012-00028-C02-02), MINECO (BFU2010-17450, ACI2009-0919, IT2009-0021, BIO2013-41019-P, LIPOCELL TT02, and TERARMET RTC-2014-2207-1), and from the Centro de Investigación Biomédica en Red (CIBER) de Bioingeniería, Biomateriales y Nanomedicina (NANOLYSO, NANOPROTHER, and PENTRI projects). CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The author is also indebted to the Protein Production Platform (CIBER-BBN/UAB) for helpful technical assistance during recombinant protein production and purification (http://www.ciber-bbn.es/en/programas/89-plataforma-de-produccion-de-proteinas).
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Corchero, J.L. Eukaryotic aggresomes: from a model of conformational diseases to an emerging type of immobilized biocatalyzers. Appl Microbiol Biotechnol 100, 559–569 (2016). https://doi.org/10.1007/s00253-015-7107-y
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DOI: https://doi.org/10.1007/s00253-015-7107-y