A curcumin-based molecular probe for near-infrared fluorescence imaging of tau fibrils in Alzheimer's disease.
In recent years, there has been growing interest in the near-infrared (NIR) fluorescence imaging of tau fibrils for the early diagnosis of Alzheimer's disease (AD). In order to develop a curcumin-based NIR fluorescent probe for tau fibrils, structural modification of the curcumin scaffold was attempted by combining the following rationales: the curcumin derivative should preserve its binding affinity to tau fibrils, and, upon binding to tau fibrils, the probe should show favorable fluorescence properties. To meet these requirements, we designed a novel curcumin scaffold with various aromatic substituents. Among the series, the curcumin derivative with a (4-dimethylamino-2,6-dimethoxy)phenyl moiety showed a significant change in its fluorescence properties (22.9-fold increase in quantum yield; Kd, 0.77 μM; λem, 620 nm; Φ, 0.32) after binding to tau fibrils. In addition, fluorescence imaging of tau-green fluorescent protein-transfected SHSY-5Y cells with confirmed that detected tau fibrils in live cells.
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Korea. chongy@konkuk.ac.kr.
Kwang-Su
KS
Park
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Korea. chongy@konkuk.ac.kr.
Yujin
Y
Seo
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Korea. chongy@konkuk.ac.kr.
Mi Kyoung
MK
Kim
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Korea. chongy@konkuk.ac.kr.
Kyungdo
K
Kim
Center for Neuro-Medicine, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seoungbuk-gu, Seoul 136-791, Korea and Department of Biological Chemistry, Korea University of Science and Technology, Youseong-gu, Daejeon 305-350, Korea.
Yun Kyung
YK
Kim
Center for Neuro-Medicine, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seoungbuk-gu, Seoul 136-791, Korea and Department of Biological Chemistry, Korea University of Science and Technology, Youseong-gu, Daejeon 305-350, Korea.
Hyunah
H
Choo
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Korea. chongy@konkuk.ac.kr.
Youhoon
Y
Chong
D000544:Alzheimer Disease / Q000175:diagnosis*; D002460:Cell Line; D003474:Curcumin / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D018613:Microscopy, Confocal; D015335:Molecular Probes / Q000737:chemistry*; D061848:Optical Imaging; D066263:Protein Aggregation, Pathological / Q000175:diagnosis*; D013055:Spectrophotometry, Infrared; D016875:tau Proteins / Q000032:analysis* / Q000648:ultrastructure
D005456:Fluorescent Dyes; D015335:Molecular Probes; D016875:tau Proteins; D003474:Curcumin