Curcumin: A multi-target disease-modifying agent for late-stage transthyretin amyloidosis

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Ferreira, N (Author) Other; Goncalves, NP (Author) Other; Maria Joao Saraiva (Author) FCUP; Almeida, MR (Author) ICBAS

Journal

Title: Scientific Reports

Vol. 6

ISSN: 2045-2322

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 34 Citations

Scopus - 36 Citations

Other information

Authenticus ID: P-00K-GAE

DOI: 10.1038/srep26623

Abstract (EN): Transthyretin amyloidoses encompass a variety of acquired and hereditary diseases triggered by systemic extracellular accumulation of toxic transthyretin aggregates 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 transthyretin oligomers 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-target disease-modifying agent for late-stage transthyretin amyloidosis.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12