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Molecular Mechanism of Apoptosis by Amyloid β‑Protein Fibrils Formed on Neuronal Cells
journal contribution
posted on 2020-02-13, 21:29 authored by Eri Takada, Kaori Okubo, Yoshiaki Yano, Keiko Iida, Masataka Someda, Akira Hirasawa, Shin Yonehara, Katsumi MatsuzakiAggregational states of amyloid β-protein
(Aβ) are
critical for its neurotoxicity, although they are not well-characterized,
particularly after binding to the cell membranes. This is one reason
why the mechanisms of Aβ neurotoxicity are controversial and
elusive. In this study, the effects of toxic Aβ-(1–42)
fibrils formed in the membrane on cellular processes were investigated
using human neuroblastoma SH-SY5Y cells. Consistent with previous
observations, fibrillar Aβs formed on the membranes induced
activation of caspase-3, the effector caspase for apoptosis. Knockdown
analyses of the initiator caspases, caspase-8 and caspase-9, indicated
that the apoptosis was induced via activation of caspase-8, followed
by activation of caspase-9 and caspase-3. We also found that inflammation
signaling pathways including Toll-like receptors and inflammasomes
NOD-, LRR-, and pyrin domain-containing protein 3 are involved in
the initiation of apoptosis by the Aβ fibrils. These inflammation-related
molecules are promising targets for the prevention of apoptotic cell
death induced by Aβ.
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Keywords
caspase -3.activationpyrin domain-containing protein 3Knockdown analysesLRRcaspase -9caspase -8inflammation-related moleculesMolecular Mechanismneuroblastoma SH-SY 5Y cellsapoptotic cell deathToll-like receptorsapoptosiNODamyloid β- proteinβ neurotoxicityNeuronal Cells Aggregational statesβ fibrilscell membraneseffector caspaseinitiator caspases
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