
In situ fibrillizing amyloid-beta 1-42 induces neurite degeneration and apoptosis of differentiated SH-SY5Y cells
Author(s) -
Jekaterina Krishtal,
Olga Bragina,
Kristel Metsla,
Peep Palumaa,
Vello Tõugu
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0186636
Subject(s) - neurite , sh sy5y , p3 peptide , fibril , microbiology and biotechnology , amyloid beta , amyloid (mycology) , cell culture , programmed cell death , chemistry , biochemistry of alzheimer's disease , apoptosis , amyloid precursor protein , peptide , alzheimer's disease , biology , in vitro , biochemistry , pathology , neuroblastoma , medicine , inorganic chemistry , disease , genetics
The progression of Alzheimer’s disease is causatively linked to the accumulation of amyloid-β aggregates in the brain, however, it is not clear how the amyloid aggregates initiate the death of neuronal cells. The in vitro toxic effects of amyloid peptides are most commonly examined using the human neuroblastoma derived SH-SY5Y cell line and here we show that differentiated neuron-like SH-SY5Y cells are more sensitive to amyloid peptides than non-differentiated cells, because the latter lack long neurites. Exogenous soluble amyloid-β 1–42 covered cell bodies and whole neurites in differentiated cells with dense fibrils, causing neurite beading and fragmentation, whereas preformed amyloid-β 1–42 fibrils had no toxic effects. Importantly, spontaneously fibrillizing amyloid-β 1–42 peptide exhibited substantially higher cellular toxicity than amyloid-β 1–40, which did not form fibrils under the experimental conditions. These results support the hypothesis that peptide toxicity is related to the active fibrillization process in the incubation mixture.