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Genistein protects against amyloid‐beta‐induced toxicity in SH‐SY5Y cells by regulation of Akt and Tau phosphorylation
Author(s) -
Petry Fernanda dos Santos,
Coelho Bárbara Paranhos,
Gaelzer Mariana Maier,
Kreutz Fernando,
Guma Fátima Theresinha Costa Rodrigues,
Salbego Christianne Gazzana,
Trindade Vera Maria Treis
Publication year - 2020
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6560
Subject(s) - neuroprotection , protein kinase b , genistein , hyperphosphorylation , tau protein , sh sy5y , gsk 3 , programmed cell death , kinase , amyloid beta , chemistry , microbiology and biotechnology , phosphorylation , pi3k/akt/mtor pathway , apoptosis , biology , pharmacology , biochemistry , endocrinology , medicine , alzheimer's disease , cell culture , neuroblastoma , peptide , genetics , disease
Alzheimer's disease is a neurodegenerative disorder characterized by extracellular deposition of amyloid‐β (Aβ) peptide and hyperphosphorylation of Tau protein, which ultimately leads to the formation of intracellular neurofibrillary tangles and cell death. Increasing evidence indicates that genistein, a soy isoflavone, has neuroprotective effects against Aβ‐induced toxicity. However, the molecular mechanisms involved in its neuroprotection are not well understood. In this study, we have established a neuronal damage model using retinoic‐acid differentiated SH‐SY5Y cells treated with different concentrations of Aβ 25–35 to investigate the effect of genistein against Aβ‐induced cell death and the possible involvement of protein kinase B (PKB, also termed Akt), glycogen synthase kinase 3β (GSK‐3β), and Tau as an underlying mechanism to this neuroprotection. Differentiated SH‐SY5Y cells were pre‐treated for 24 hr with genistein (1 and 10 nM) and exposed to Aβ 25–35 (25 μM), and we found that genistein partially inhibited Aβ induced cell death, primarily apoptosis. Furthermore, the protective effect of genistein was associated with the inhibition of Aβ‐induced Akt inactivation and Tau hyperphosphorylation. These findings reinforce the neuroprotective effects of genistein against Aβ toxicity and provide evidence that its mechanism may involve regulation of Akt and Tau proteins.