Abstract
The isoflavone, genistein, present in soybean is being actively investigated for its potential beneficial effect against Alzheimer's disease. Our data, however, show that in SHSY5Y cells genistein causes increased expression (mRNA and protein) of amyloid precursor protein (APP), increased mRNA expression and activity of β-secretase and diminished level of insulin degrading enzyme (IDE) which also degrades amyloid beta peptide. These effects of genistein lead to enhanced accumulation of amyloid beta peptide (Aβ42) in SHSY5Y cells. The results do not support the view that genistein could be a putative drug against AD and instead strengthen the epidemiological study which implies that genistein content of soybean food product (Tofu) leads to cognitive impairment.
Highlights
The isoflavone, genistein, present in soybean is being actively investigated for its potential beneficial effect against Alzheimer’s disease
The β-secretase mRNA expression in SHSY5Y cells was modestly upregulated in the concentration range of 10 – 30 μM of genistein with a maximum of 1.8 fold increase noticed at 20 μM concentration with respect to control (Fig. 2A)
We have clearly demonstrated that genistein has a dose-dependent stimulatory effect on several aspects of amyloid beta peptide synthesis in SHSY5Y cells
Summary
The isoflavone, genistein, present in soybean is being actively investigated for its potential beneficial effect against Alzheimer’s disease. Show that in SHSY5Y cells genistein causes increased expression (mRNA and protein) of amyloid precursor protein (APP), increased mRNA expression and activity of β-secretase and diminished level of insulin degrading enzyme (IDE) which degrades amyloid beta peptide. Genistein and amyloid beta peptide has reported that mid-life high intake of Tofu (soybean curd) is associated with increased risk of dementia which could be attributed to high content of isoflavones, in particular genistein, in Tofu [14]. Another cross-sectional study in Indonesia has linked poor memory performance with high Tofu intake [15]. SHSY5Y cells have been used extensively to study amyloid precursor protein (APP) expression, processing and trafficking and amyloid beta peptide homeostasis within cells, and further these cells, both undifferentiated or differentiated by retinoic acid treatment, serve as a useful tool for elucidation of the pathways of neurodegeneration induced by various toxic agents including amyloid beta [19, 20, 21]
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