Please use this identifier to cite or link to this item: http://hdl.handle.net/10216/108248
Author(s): Ferreira, N
Gonçalves, NP
Saraiva, MJ
Almeida, M
Title: Curcumin: A multi-Target disease-modifying agent for late-stage transthyretin amyloidosis
Publisher: Nature Publishing Group
Issue Date: 2016
Abstract: Transthyretin amyloidoses encompass a variety of acquired and hereditary diseases triggered by systemic extracellular accumulation of toxic transthyretinaggregates and fibrils, particularly in the peripheral nervous system. Since transthyretin amyloidoses are typically complex progressive disorders, therapeutic approaches aiming multiple molecular targets simultaneously, might improve therapy efficacy and treatment outcome. In this study, we evaluate the protective effect of physiologically achievable doses of curcumin on the cytotoxicity induced by transthyretin oligomers in vitro by showing reduction of caspase-3 activity and the levels of endoplasmic reticulum-resident chaperone binding immunoglobulin protein. When given to an aged Familial Amyloidotic Polyneuropathy mouse model, curcumin not only reduced transthyretin aggregates deposition and toxicity in both gastrointestinal tract and dorsal root ganglia but also remodeled congophilic amyloid material in tissues. In addition, curcumin enhanced internalization, intracellular transport and degradation of transthyretinoligomers by primary macrophages from aged Familial Amyloidotic Polyneuropathy transgenic mice, suggesting an impaired activation of naive phagocytic cells exposed to transthyretin toxic intermediate species. Overall, our results clearly support curcumin or optimized derivatives as promising multi-targetdisease-modifying agent for late-stage transthyretin amyloidosis.
Subject: Endoplasmic-reticulum stress
Alzheimers-disease
Mouse model
Fibril formation
Congo red
In-vivo
Polyneuropathy
Deposition
Internalization
Neurotoxicity
URI: http://hdl.handle.net/10216/108248
Source: Scientific Reports, vol. 6:26623
Related Information: info:eu-repo/grantAgreement/FCT/5876-PPCDTI/116645/PT
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
License: http://creativecommons.org/licenses/by/4.0/
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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