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Uncovering the Neuroprotective Mechanisms of Curcumin on Transthyretin Amyloidosis

1
Danish Research Institute of Translational Neuroscience, Nordic EMBL Partnership for Molecular Medicine, Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark
2
Molecular Neurobiology Group, IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal
3
Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, 4200-135 Porto, Portugal
4
Molecular Biology Department, ICBAS-Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(6), 1287; https://doi.org/10.3390/ijms20061287
Received: 15 February 2019 / Revised: 2 March 2019 / Accepted: 7 March 2019 / Published: 14 March 2019
(This article belongs to the Special Issue Curcumin in Health and Disease)
Transthyretin (TTR) amyloidoses (ATTR amyloidosis) are diseases associated with transthyretin (TTR) misfolding, aggregation and extracellular deposition in tissues as amyloid. Clinical manifestations of the disease are variable and include mainly polyneuropathy and/or cardiomyopathy. The reasons why TTR forms aggregates and amyloid are related with amino acid substitutions in the protein due to mutations, or with environmental alterations associated with aging, that make the protein more unstable and prone to aggregation. According to this model, several therapeutic approaches have been proposed for the diseases that range from stabilization of TTR, using chemical chaperones, to clearance of the aggregated protein deposited in tissues in the form of oligomers or small aggregates, by the action of disruptors or by activation of the immune system. Interestingly, different studies revealed that curcumin presents anti-amyloid properties, targeting multiple steps in the ATTR amyloidogenic cascade. The effects of curcumin on ATTR amyloidosis will be reviewed and discussed in the current work in order to contribute to knowledge of the molecular mechanisms involved in TTR amyloidosis and propose more efficient drugs for therapy. View Full-Text
Keywords: curcumin; transthyretin; amyloidosis; protein aggregation; protein misfolding; drug discovery curcumin; transthyretin; amyloidosis; protein aggregation; protein misfolding; drug discovery
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Ferreira, N.; Saraiva, M.J.; Almeida, M.R. Uncovering the Neuroprotective Mechanisms of Curcumin on Transthyretin Amyloidosis. Int. J. Mol. Sci. 2019, 20, 1287.

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