期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 20, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/ijms20061287
关键词
curcumin; transthyretin; amyloidosis; protein aggregation; protein misfolding; drug discovery
资金
- European Regional Development Fund (FEDER) through the Norte Portugal Regional Operational Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement [Norte-01-0145-FEDER-000008]
- Lundbeck foundation [R171-2014-591, R248-2016-2518]
- Lundbeck Foundation [R248-2016-2518] Funding Source: researchfish
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.
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