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language
eng
Author
Tabassum, Shatera
Description
Amyloid β (Aβ), a 39-42 amino acid peptide derived from amyloid precursor protein, is deposited as fibrils in Alzheimer's disease brains, and is considered to play a major role in the pathogenesis of the disease. We have investigated the effects of a water-soluble Zn-phthalocyanine, ZnPc(COONa)_8, a macrocyclic compound with near-infrared optical properties, on Aβ fibril formation in vitro. A thioflavin T fluorescence assay showed that ZnPc(COONa)_8 significantly inhibited Aβ fibril formation, increasing the lag time and dose-dependently decreasing the plateau level of fibril formation. Moreover, it destabilized pre-formed Aβ fibrils, resulting in an increase in low-molecular-weight species. After fibril formation in the presence of ZnPc(COONa)_8, immunoprecipitation of Aβ_<1-42> using Aβ-specific antibody followed by near-infrared scanning demonstrated binding of ZnPc(COONa)_8 to Aβ_<1-42>. A study using the hydrophobic fluorescent probe 8-anilino-1-naphthalenesulfonic acid showed that ZnPc(COONa)_8 decreased the hydrophobicity during Aβ_<1-42> fibril formation. CD spectroscopy showed an increase in the α helix structure and a decrease in the β sheet structure of Aβ_<1-40> in fibril-forming buffer containing ZnPc(COONa)_8. SDS/PAGE and a dot-blot immunoassay showed that ZnPc(COONa)_8 delayed the disappearance of low-molecular-weight species and the appearance of higher-molecular-weight oligomeric species of Aβ_<1-42>. A cell viability assay showed that ZnPc(COONa)_8 was not toxic to a neuronal cell line (A1), but instead protected A1 cells against Aβ_<1-42>-induced toxicity. Overall, our results indicate that ZnPc(COONa)_8 binds to Aβ and decreases the hydrophobicity, and this change is unfavorable for Aβ oligomerization and fibril formation.
Subject
Alzheimer's disease
amyloid β peptide
fibril formation
near infrared
phthalocyanine
Journal Title
The FEBS journal
Volume
282
Issue
3
Start Page
463
End Page
476
ISSN
1742464X
Published Date
2015-02
DOI
DOI Date
2017-06-01
PubMed ID
NCID
AA11998513
Publisher
Wiley
NII Type
Journal Article
Format
PDF
Rights
This is the peer reviewed version of the following article:Tabassum S, Sheikh AM, Yano S, Ikeue T, Handa M, Nagai A.(2015), A carboxylated Zn-phthalocyanine inhibits fibril formation of Alzheimer's amyloid β peptide. FEBS Journal, 282: 463-476, which has been published in final form at http://dx.doi.org/10.1111/febs.13151. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Text Version
著者版
Gyoseki ID
e29000
e29548
e28576
OAI-PMH Set
Faculty of Medicine
Interdisciplinary Graduate School of Science and Engineering