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A carboxylated Zn‐phthalocyanine inhibits fibril formation of Alzheimer's amyloid β peptide
Author(s) -
Tabassum Shatera,
Sheikh Abdullah M.,
Yano Shozo,
Ikeue Takafumi,
Handa Makoto,
Nagai Atsushi
Publication year - 2015
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13151
Subject(s) - fibril , thioflavin , chemistry , peptide , biophysics , amyloid (mycology) , fluorescence , phthalocyanine , biochemistry , alzheimer's disease , biology , organic chemistry , pathology , medicine , inorganic chemistry , physics , disease , quantum mechanics
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( COON a) 8 , a macrocyclic compound with near‐infrared optical properties, on Aβ fibril formation in vitro . A thioflavin T fluorescence assay showed that ZnPc( COON a) 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( COON a) 8 , immunoprecipitation of Aβ 1‐42 using Aβ‐specific antibody followed by near‐infrared scanning demonstrated binding of ZnPc( COON a) 8 to Aβ 1‐42 . A study using the hydrophobic fluorescent probe 8‐anilino‐1‐naphthalenesulfonic acid showed that ZnPc( COON a) 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( COON a) 8 . SDS/PAGE and a dot‐blot immunoassay showed that ZnPc( COON a) 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( COON a) 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( COON a) 8 binds to Aβ and decreases the hydrophobicity, and this change is unfavorable for Aβ oligomerization and fibril formation.