TY - JOUR
T1 - Toxic Tau Oligomers Modulated by Novel Curcumin Derivatives
AU - Lo Cascio, Filippa
AU - Puangmalai, Nicha
AU - Ellsworth, Anna
AU - Bucchieri, Fabio
AU - Pace, Andrea
AU - Palumbo Piccionello, Antonio
AU - Kayed, Rakez
N1 - Funding Information:
We Thank Omar D. Johnson and Cynthia A. Duarte for editing the manuscript. We are grateful to Dr. Urmi Sengupta for useful suggestions and the members of the Kayed Lab for their help. This research work was supported by Mitchell Center for Neurodegenerative Diseases, the Gillson Longenbaugh Foundation and National Institute of Health grants: R01AG054025, R01NS094557, RFA1AG055771, R01AG060718 and the American Heart Association collaborative grant 17CSA33620007 (R.K.). F.L.C. was also supported by UTMB-University of Palermo joint PhD program.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - The pathological aggregation and accumulation of tau, a microtubule-associated protein, is a common feature amongst more than 18 different neurodegenerative diseases that are collectively known as tauopathies. Recently, it has been demonstrated that the soluble and hydrophobic tau oligomers are highly toxic in vitro due to their capacity towards seeding tau misfolding, thereby propagating the tau pathology seen across different neurodegenerative diseases. Modulating the aggregation state of tau oligomers through the use of small molecules could be a useful therapeutic strategy to target their toxicity, regardless of other factors involved in their formation. In this study, we screened and tested a small library of newly synthesized curcumin derivatives against preformed recombinant tau oligomers. Our results show that the curcumin derivatives affect and modulate the tau oligomer aggregation pathways, converting to a more aggregated non-toxic state as assessed in the human neuroblastoma SH-SY5Y cell line and primary cortical neuron cultures. These results provide insight into tau aggregation and may become a basis for the discovery of new therapeutic agents, as well as advance the diagnostic field for the detection of toxic tau oligomers.
AB - The pathological aggregation and accumulation of tau, a microtubule-associated protein, is a common feature amongst more than 18 different neurodegenerative diseases that are collectively known as tauopathies. Recently, it has been demonstrated that the soluble and hydrophobic tau oligomers are highly toxic in vitro due to their capacity towards seeding tau misfolding, thereby propagating the tau pathology seen across different neurodegenerative diseases. Modulating the aggregation state of tau oligomers through the use of small molecules could be a useful therapeutic strategy to target their toxicity, regardless of other factors involved in their formation. In this study, we screened and tested a small library of newly synthesized curcumin derivatives against preformed recombinant tau oligomers. Our results show that the curcumin derivatives affect and modulate the tau oligomer aggregation pathways, converting to a more aggregated non-toxic state as assessed in the human neuroblastoma SH-SY5Y cell line and primary cortical neuron cultures. These results provide insight into tau aggregation and may become a basis for the discovery of new therapeutic agents, as well as advance the diagnostic field for the detection of toxic tau oligomers.
UR - http://www.scopus.com/inward/record.url?scp=85076411660&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076411660&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-55419-w
DO - 10.1038/s41598-019-55419-w
M3 - Article
C2 - 31831807
AN - SCOPUS:85076411660
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 19011
ER -